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WUSTL Neuroscience Publications Archive - September 2014

September 2014

Scopus weekly report

September 24

September 9

September 2

September 24, 2014

Zhang, G.a , Liang, H.a , Yang, J.a , Shi, J.a , McFarland, K.a , Cui, J.a , Zhang, G.b , Cui, J.b c , Chen, Y.d
A charged residue in S4 regulates coupling among the activation gate, voltage, and Ca2+ sensors in BK channels
(2014) Journal of Neuroscience, 34 (37), pp. 12280-12288. 


a Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington UniversitySt. Louis, MO, United States
b Department of Pharmacology, Soochow University College of Pharmaceutical SciencesSuzhou, China
c Department of Physiology, University of California at San FranciscoSan Francisco, CA, United States
d Key Laboratory of Basic Research in Cardiology of the Ministry of Education of China, Tongji UniversityShanghai, China


Abstract
Coupling between the activation gate and sensors of physiological stimuli during ion channel activation is an important, but not well-understood, molecular process. One difficulty in studying sensor–gate coupling is to distinguish whether a structural perturbation alters the function of the sensor, the gate, or their coupling. BK channels are activated by membrane voltage and intracellular Ca2+ via allosteric mechanisms with coupling among the activation gate and sensors quantitatively defined, providing an excellent model system for studying sensor–gate coupling. By studying BK channels expressed in Xenopus oocytes, here we show that mutation E219R in S4 alters channel function by two independent mechanisms: one is to change voltage sensor activation, shifting voltage dependence, and increase valence of gating charge movements; the other is to regulate coupling among the activation gate, voltage sensor, and Ca2+ binding via electrostatic interactions with E321/E324 located in the cytosolic side of S6 in a neighboring subunit, resulting in a shift of the voltage dependence of channel opening and increased Ca2+ sensitivity. These results suggest a structural arrangement of the inner pore of BK channels differing from that in other voltage gated channels.


Author Keywords
BK channels;  Coupling;  Intersubunit interaction;  Pore-gate;  Voltage sensor


Document Type: Article
Source: Scopus

Zhao, Z.-Q.a , Wan, L.a , Liu, X.-Y.a , Huo, F.-Q.a , Li, H.a , Barry, D.M.a , Kim, S.a , Liu, Z.-C.a , Chen, Z.-F.a , Zhao, Z.-Q.b , Wan, L.b , Liu, X.-Y.b , Huo, F.-Q.b , Li, H.b , Barry, D.M.b , Kim, S.b , Liu, Z.-C.b , Chen, Z.-F.b , Chen, Z.-F.c , Chen, Z.-F.d , Krieger, S.e , Rogers, B.E.e , Xu, J.f , Wan, L.g , Li, H.h , Li, Y.-Q.h , Kim, S.i , Liu, Z.-C.j , Huo, F.-Q.k
Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission
(2014) Journal of Neuroscience, 34 (37), pp. 12402-12414. 


a Center for the Study of Itch, Washington University School of MedicineSt. Louis, MO, United States
b Department of Anesthesiology, Washington University School of MedicineSt. Louis, MO, United States
c Department of Psychiatry, Washington University School of MedicineSt. Louis, MO, United States
d Department of Developmental Biology, Washington University School of MedicineSt. Louis, MO, United States
e Department of Radiation Oncology, Washington University School of MedicineSt. Louis, MO, United States
f Department of Radiology, Washington University School of MedicineSt. Louis, MO, United States
g Department of Anesthesiology, The Second Affiliated Hospital, Guangzhou Medical UniversityGuangzhou, Guangdong, China
h Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, The Fourth Military Medical UniversityXi’an, Shaanxi, China
i Department of Cell and Tissue Biology, Craniofacial and Mesenchymal Biology, University of CaliforniaSan Francisco, CA, United States
j Department of Psychiatry, Renmin Hospital, Wuhan UniversityWuhan, China
k Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of MedicineXi’an, Shaanxi, China


Abstract
We previously showed that gastrin-releasing peptide receptor (GRPR) in the spinal cord is important for mediating nonhistaminergic itch. Neuromedin B receptor (NMBR), the second member of the mammalian bombesin receptor family, is expressed in a largely nonoverlapping pattern with GRPR in the superficial spinal cord, and its role in itch transmission remains unclear. Here, we report that Nmbr knock-out (KO) mice exhibited normal scratching behavior in response to intradermal injection of pruritogens. However, mice lacking both Nmbr and Grpr (DKO mice) showed significant deficits in histaminergic itch. In contrast, the chloroquine (CQ)-evoked scratching behavior of DKO mice is not further reduced compared with Grpr KO mice. These results suggest that NMBR and GRPR could compensate for the loss of each other to maintain normal histamine-evoked itch, whereas GRPR is exclusively required for CQ-evoked scratching behavior. Interestingly, GRPR activity is enhanced in Nmbr KO mice despite the lack of upregulation of Grpr expression; so is NMBR in Grpr KO mice. We found that NMB acts exclusively through NMBR for itch transmission, whereas GRP can signal through both receptors, albeit to NMBR to a much lesser extent. Although NMBR and NMBR+ neurons are dispensable for histaminergic itch, GRPR+ neurons are likely to act downstream of NMBR+ neurons to integrate NMB-NMBR-encoded histaminergic itch information in normal physiological conditions. Together, we define the respective function of NMBR and GRPR in itch transmission, and reveal an unexpected relationship not only between the two receptors but also between the two populations of interneurons in itch signaling.


Author Keywords
Cross-inhibition;  GRP;  GRPR;  Itch;  NMB;  NMBR


Document Type: Article
Source: Scopus

Sun, T.a , Warrington, N.M.a , Luo, J.b , Brooks, M.D.a , Dahiya, S.c , Snyder, S.C.a , Sengupta, R.a , Rubin, J.B.a d
Sexually dimorphic RB inactivation underlies mesenchymal glioblastoma prevalence in males
(2014) Journal of Clinical Investigation, 124 (9), pp. 4123-4133. 


a Department of Pediatrics, Washington University School of MedicineSt. Louis, MO, United States
b Division of Biostatistics, Washington University School of MedicineSt. Louis, MO, United States
c Department of Pathology and Immunology, Washington University School of MedicineSt. Louis, MO, United States
d Department of Anatomy and Neurobiology, Washington University School of MedicineSt. Louis, MO, United States


Abstract
The prevalence of brain tumors in males is common but unexplained. While sex differences in disease are typically mediated through acute sex hormone actions, sex-specific differences in brain tumor rates are comparable at all ages, suggesting that factors other than sex hormones underlie this discrepancy. We found that mesenchymal glioblastoma (Mes-GBM) affects more males as the result of cell-intrinsic sexual dimorphism in astrocyte transformation. We used astrocytes from neurofibromin-deficient (Nf1-/-) mice expressing a dominant-negative form of the tumor suppressor p53 (DNp53) and treated them with EGF as a Mes-GBM model. Male Mes-GBM astrocytes exhibited greater growth and colony formation compared with female Mes-GBM astrocytes. Moreover, male Mes-GBM astrocytes underwent greater tumorigenesis in vivo, regardless of recipient mouse sex. Male Mes-GBM astrocytes exhibited greater inactivation of the tumor suppressor RB, higher proliferation rates, and greater induction of a clonogenic, stem-like cell population compared with female Mes-GBM astrocytes. Furthermore, complete inactivation of RB and p53 in Mes-GBM astrocytes resulted in equivalent male and female tumorigenic transformation, indicating that intrinsic differences in RB activation are responsible for the predominance of tumorigenic transformation in male astrocytes. Together, these results indicate that cell-intrinsic sex differences in RB regulation and stem-like cell function may underlie the predominance of GBM in males.

 


Document Type: Article
Source: Scopus

September 9, 2014

Brenner, D.S.a b c , Golden, J.P.a , Vogt, S.K.a , Dhaka, A.d e , Story, G.M.a , Gereau IV, R.W.a b
A dynamic set point for thermal adaptation requires phospholipase C-mediated regulation of TRPM8 in vivo
(2014) Pain, . Article in Press. 


a Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA
b Neuroscience Program, Washington University School of Medicine, St. Louis, MO 63110, USA
c Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA
d Department of Biological Structure University of Washington, Seattle, WA 98195, USA
e Neurobiology and Behavior Graduate Program, University of Washington, Seattle, WA 98195, USA


Abstract
The ability to sense and respond to thermal stimuli at varied environmental temperatures is essential for survival in seasonal areas. In this study, we show that mice respond similarly to ramping changes in temperature from a wide range of baseline temperatures. Further investigation suggests that this ability to adapt to different ambient environments is based on rapid adjustments made to a dynamic temperature set point. The adjustment of this set point requires transient receptor potential cation channel, subfamily member 8 (TRPM8), but not transient receptor potential cation channel, subfamily A, member 1 (TRPA1), and is regulated by phospholipase C (PLC) activity. Overall, our findings suggest that temperature response thresholds in mice are dynamic, and that this ability to adapt to environmental temperature seems to mirror the in vitro findings that PLC-mediated hydrolysis of phosphoinositol 4,5-bisphosphate modulates TRPM8 activity and thereby regulates the response thresholds to cold stimuli. © 2014 International Association for the Study of Pain.


Author Keywords
Adaptation;  Cold;  Heat;  Pain;  Phospholipase C;  PIP2;  Thermosensation;  TRPA1;  TRPM8


Document Type: Article in Press
Source: Scopus

Kress, G.J.a , Shu, H.-J.a , Yu, A.a , Taylor, A.a , Benz, A.a , Harmon, S.b , Mennerick, S.a b c
Fast phasic release properties of dopamine studied with a channel biosensor
(2014) Journal of Neuroscience, 34 (35), pp. 11792-11802. 


a Departments of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States
b Departments of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO 63110, United States


Abstract
Few other neurotransmitters are of as intense interest to neuropsychiatry and neurology as dopamine, yet existing techniques to monitor dopamine release leave an important spatiotemporal gap in our understanding. Electrochemistry and fluorescence imaging tools have been developed to fill the gap, but these methods have important limitations. We circumvent these limitations by introducing a dopamine-gated chloride channel into rat dorsal striatal medium spiny neurons, targets of strong dopamine innervation, thereby transforming dopamine from a slow transmitter into a fast transmitter and revealing new opportunities for studying moment-to-moment regulation of dopamine release. We demonstrate pharmacological and biophysical properties of the channel that make it suitable for fast, local dopamine measurements, and we demonstrate for the first time spontaneous and evoked responses to vesicular dopamine release in the dorsal striatum. Evoked dopamine currents were separated into a fast, monosynaptic component and a slower-rising and decaying disynaptic component mediated by nicotinic receptor activation. In summary, LGC-53 represents a dopamine biosensor with properties suitable for temporal separation of distinct dopamine signals in targets of dopamine innervation. © 2014 the authors.


Author Keywords
Dopamine release;  Ligand-gated ion channel;  Nicotinic;  Presynaptic;  Striatum


Document Type: Article
Source: Scopus

Raghuraman, A.P.a , Padoa-Schioppa, C.a b c
Integration of multiple determinants in the neuronal computation of economic values
(2014) Journal of Neuroscience, 34 (35), pp. 11583-11603. 


a Departments of Anatomy and Neurobiology, Washington University in St Louis, St Louis, MO 63110, United States
b Departments of Economics, Washington University in St Louis, St Louis, MO 63110, United States
c Departments of Biomedical Engineering, Washington University in St Louis, St Louis, MO 63110, United States


Abstract
Economic goods may vary on multiple dimensions (determinants). A central conjecture in decision neuroscience is that choices between goods are made by comparing subjective values computed through the integration of all relevant determinants. Previous work identified three groups of neurons in the orbitofrontal cortex (OFC) of monkeys engaged in economic choices: (1) offer value cells, which encode the value of individual offers; (2) chosen value cells, which encode the value of the chosen good; and (3) chosen juice cells, which encode the identity of the chosen good. In principle, these populations could be sufficient to generate a decision. Critically, previous work did not assess whether offer value cells (the putative input to the decision) indeed encode subjective values as opposed to physical properties of the goods, and/or whether offer value cells integrate multiple determinants. To address these issues, we recorded from the OFC while monkeys chose between risky outcomes. Confirming previous observations, three populations of neurons encoded the value of individual offers, the value of the chosen option, and the value-independent choice outcome. The activity of both offer value cells and chosen value cells encoded values defined by the integration of juice quantity and probability. Furthermore, both populations reflected the subjective risk attitude of the animals. We also found additional groups of neurons encoding the risk associated with a particular option, the risky nature of the chosen option, and whether the trial outcome was positive or negative. These results provide substantial support for the conjecture described above and for the involvement of OFC in good-based decisions. © 2014 the authors.


Author Keywords
Economic choice;  Neuroeconomics;  Orbitofrontal cortex;  Primate neurophysiology;  Rhesus monkey;  Subjective value


Document Type: Article
Source: Scopus

Mccreedy, D.A.a , Brown, C.R.a , Butts, J.C.a , Xu, H.a , Huettner, J.E.b , Sakiyama-Elbert, S.E.a
A new method for generating high purity motoneurons from mouse embryonic stem cells
(2014) Biotechnology and Bioengineering, 111 (10), pp. 2041-2055. 


a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
A common problem with using embryonic stem (ES) cells as a source for analysis of gene expression, drug toxicity, or functional characterization studies is the heterogeneity that results from many differentiation protocols. The ability to generate large numbers of high purity differentiated cells from pluripotent stem cells could greatly enhance their utility for in vitro characterization studies and transplantation in pre-clinical injury models. Population heterogeneity is particularly troublesome for post-mitotic neurons, including motoneurons, because they do not proliferate and are quickly diluted in culture by proliferative phenotypes, such as glia. Studies of motoneuron biology and disease, in particular amyotrophic lateral sclerosis, can benefit from high purity motoneuron cultures. In this study, we engineered a transgenic-ES cell line where highly conserved enhancer elements for the motoneuron transcription factor Hb9 were used to drive puromycin N-acetyltransferase expression in ES cell-derived motoneurons. Antibiotic selection with puromycin was then used to obtain high purity motoneuron cultures following differentiation of mouse ES cells. Purity was maintained during maturation allowing the production of consistent, uniform populations of cholinergic ES cell-derived motoneurons. Appropriate functional properties of purified motoneurons were verified by acetylcholinesterase activity and electrophysiology. Antibiotic selection, therefore, can provide an inexpensive alternative to current methods for isolating ES cell-derived motoneurons at high purity that does not require specialized laboratory equipment and provides a unique platform for studies in motoneuron development and degeneration. © 2014 Wiley Periodicals, Inc.


Author Keywords
Electrophysiology;  Neural differentiation;  Puromycin selection;  Transcription factor


Document Type: Article
Source: Scopus

Larson-Prior, L.J.a b , Ju, Y.-E.b , Galvin, J.E.c d e
Cortical-subcortical interactions in hypersomnia disorders: Mechanisms underlying cognitive and behavioral aspects of the sleep-wake cycle
(2014) Frontiers in Neurology, 5 AUG, art. no. Article 165, . 


a Departments of Radiology, Washington University School of Medicine, St. Louis, MO, United States
b Departments of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurology, New York University, Langone School of Medicine, New York, NY, United States
d Department of Psychiatry, New York University, Langone School of Medicine, New York, NY, United States
e Department of Population Health, New York University, Langone School of Medicine, New York, NY, United States


Abstract
Subcortical circuits mediating sleep-wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders such as narcolepsy and Klein- Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep-wake functions is not a simple on-or-offstate determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, hypersomnia disorders are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where EEG demonstrates abnormal function in cortical regions associated with cognitive fluctuations. Moreover, functional connectivity MRI shows instability of cortical networks in individuals with cognitive fluctuations. We propose that the inability to stabilize neural state due to disruptions in the sleep-wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders. © 2014 Larson-prior, Ju and Galvin.


Author Keywords
Brain networks;  Cognitive fluctuations;  Hypersomnia;  Review;  Sleep


Document Type: Article
Source: Scopus

Murray, M.a , Stanley, M.b , Lugar, H.M.a , Hershey, T.c
Hippocampal volume in type 1 diabetes
(2014) European Endocrinology, 10 (1), pp. 14-17. 


a Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
c Departments of Psychiatry, Neurology and Radiology, Washington University School of Medicine, St Louis, MO, United States


Abstract
The hippocampus plays an important role in human memory and is known to be vulnerable to extreme hyperglycaemia and hypoglycaemia in animal models of type 1 diabetes. Within humans with type 1 diabetes, exposure to glycaemic extremes has been associated with alterations in hippocampal structure and in memory function, but results are inconsistent. It has been hypothesised that the effects of hypoglycaemia and hyperglycaemia on the hippocampus may depend on when during neurodevelopment these extremes occur, possibly explaining some of these inconsistencies. However, data addressing this concept are limited. We review here the existing literature on this complex topic and suggest future avenues of required research.


Author Keywords
Brain;  Development;  Diabetes;  Hippocampus;  Hyperglycaemia;  Hypoglycaemia


Document Type: Article
Source: Scopus

Stevens, M.N., Hullar, T.E.
Improvement in sensorineural hearing loss during pregnancy
(2014) Annals of Otology, Rhinology and Laryngology, 123 (9), pp. 614-618. 


Department of Otolaryngology-Head and Neck Surgery, Washington University, School of Medicine, 660 South Euclid Avenue #8115, St. Louis, MO 63110, United States


Abstract
Objective: Hearing loss is known to occur in some pregnant women, but improvement in sensorineural thresholds has not been audiometrically characterized. Here, we describe a patient with a history of Ménière's disease and vestibular migraine who experienced temporary recovery of her hearing during pregnancy. Methods: Audiograms were obtained from a 31-year-old female over the course of 2 successive pregnancies. Results: Audiograms revealed a substantial improvement in hearing by the third trimester during each pregnancy, with a rapid return to baseline thresholds after delivery. Conclusion: This case is unique in documenting improvements in hearing thresholds during pregnancy and substantiates the effects of hormonal changes on hearing thresholds in humans. It raises the intriguing possibility of hormonal therapy as a treatment for sensorineural hearing loss in specific clinical situations. © The Author(s) 2014.


Author Keywords
Audiogram;  Auditory;  Hearing;  Hormone;  Ménière's;  Migraine;  Pregnancy;  Threshold;  Vestibular


Document Type: Article
Source: Scopus

Schürks, M.a , Winter, A.b , Berger, K.c , Kurth, T.d e f g
Migraine and restless legs syndrome: A systematic review
(2014) Cephalalgia, 34 (10), pp. 777-794. 


a Department of Neurology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany
b Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
c Institute of Epidemiology and Social Medicine, University of Münster, Germany
d Division of Preventive Medicine, Department of Medicine, Boston, MA, United States
e Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
f College of Health Sciences, University of Bordeaux, France
g Inserm Research Center for Epidemiology and Biostatistics, Team Neuroepidemiology, Bordeaux, France


Abstract
Background: Restless legs syndrome (RLS) is increasingly being reported as a comorbidity of migraine. Methods: We conducted a systematic review and meta-analysis of studies investigating RLS in headache/migraine and vice versa.We calculated the prevalence and 95% confidence intervals (CI) of RLS in headache/migraine, of headache/migraine in RLS and controls, and odds ratios (ORs) of the association between the conditions.We then determined pooled effect estimates for the associations. Results: We identified 24 studies. RLS prevalence in migraine ranged from 8.7% to 39.0% with no apparent differences based on gender and aura status. Prevalence among controls was compatible with the literature. Migraine prevalence in RLS ranged from 15.1% to 62.6%. We did not pool prevalence data because of high unexplained heterogeneity. High heterogeneity with respect to the association between any migraine and RLS could be explained by study design. Pooled analyses showed substantially higher effect estimates in case-control studies (pooled OR=4.19, 95% CI 3.07±5.71; I2=0.0%) than in cohort studies (pooled OR=1.22, 95% CI 1.14±1.30; I2=0.0%). Conclusion: Our results support the concept of RLS as an important comorbidity of migraine. However, the degree of association appears to be strongly determined by study design. Potential effects by gender and aura status and the role of RLS in other headache disorders remain unclear. © International Headache Society 2014.


Author Keywords
Association;  Meta-analysis;  Migraine;  Prevalence;  Restless legs syndrome;  Systematic review


Document Type: Review
Source: Scopus

Prather, H.a , Camacho-Soto, A.b
Musculoskeletal etiologies of pelvic pain
(2014) Obstetrics and Gynecology Clinics of North America, 41 (3), pp. 433-442. 


a Section of Physical Medicine and Rehabilitation, Department of Orthopaedic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box8233, StLouis, MO 63110, United States
b Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine/Rehabilitation Institute of Chicago, 345 East Superior Street, Chicago, IL 60611, United States


Abstract
Several musculoskeletal diagnoses are frequently concomitant with pelvic floor pathology and pain. The definition of pelvic pain itself often depends on the medical specialist evaluating the patient. Because there is variability among disorders associated with pelvic pain, patients may seek treatment for extended periods as various treatment options are attempted. Further, health care providers should recognize that there may not be a single source of dysfunction. This article discusses the musculoskeletal disorders of the pelvic girdle (structures within the bony pelvis) and their association with lumbar spine and hip disorders. © 2014 Elsevier Inc.


Author Keywords
Lumbar spine;  Musculoskeletal;  Pelvic girdle;  Pelvic pain


Document Type: Review
Source: Scopus

Spitznagle, T.M.a , McCurdy Robinson, C.b
Myofascial pelvic pain
(2014) Obstetrics and Gynecology Clinics of North America, 41 (3), pp. 409-432. 


a Washington University School of Medicine, 4444 Forest Park, Box 8502, St Louis, MO 63108-2212, United States
b Sullivan Physical Therapy, Austin, TX 78750, United States


Abstract
Individuals with pelvic pain commonly present with complaints of pain located anywhere below the umbilicus radiating to the top of their thighs or genital region. The somatovisceral convergence that occurs within the pelvic region exemplifies why examination of not only the organs but also the muscles, connective tissues (fascia), and neurologic input to the region should be performed for women with pelvic pain. The susceptibility of the pelvic floor musculature to the development of myofascial pain has been attributed to unique functional demands of this muscle. Conservative interventions should be considered to address the impairments found on physical examination. © 2014 Elsevier Inc.


Author Keywords
Myofascial pain syndrome;  Pelvic pain;  Somatovisceral convergence


Document Type: Review
Source: Scopus

Holy, T.E.
Scenting Waldo: Analyzing olfactory scenes
(2014) Nature Neuroscience, 17 (9), pp. 1144-1145. 


Department of Anatomy AndNeurobiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States


Document Type: Note
Source: Scopus

Lord, J.a , Cruchaga, C.a b
The epigenetic landscape of Alzheimer's disease
(2014) Nature Neuroscience, 17 (9), pp. 1138-1140. 


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, MO, United States


Document Type: Note
Source: Scopus

Chang, N.-Y.N.a , Hiss, M.M.a , Sanders, M.C.a , Olomu, O.U.a , MacNeilage, P.R.b , Uchanski, R.M.a , Hullar, T.E.a
Vestibular perception and the vestibulo-ocular reflex in young and older adults
(2014) Ear and Hearing, 35 (5), pp. 565-570. 


a Department of Otolaryngology-Head and Neck Surgery, Washington University, School of Medicine, 660 South Euclid Avenue #8115, St. Louis, MO 63110, United States
b Department of Neurology, Ludwig-Maximilians-Universität, Munich, Germany


Abstract
OBJECTIVES:: Quantification of the perceptual thresholds to vestibular stimuli may offer valuable complementary information to that provided by measures of the vestibulo-ocular reflex (VOR). Perceptual thresholds could be particularly important in evaluating some subjects, such as the elderly, who might have a greater potential of central as well as peripheral vestibular dysfunction. The authors hypothesized that perceptual detection and discrimination thresholds would worsen with aging, and that there would be a poor relation between thresholds and traditional measures of the angular VOR represented by gain and phase on rotational chair testing. DESIGN:: The authors compared the detection and discrimination thresholds of 19 younger and 16 older adults in response to earth-vertical, 0.5 Hz rotations. Perceptual results of the older subjects were then compared with the gain and phase of their VOR in response to earth-vertical rotations over the frequency range from 0.025 to 0.5 Hz. RESULTS:: Detection thresholds were found to be 0.69 ± 0.29 degree/sec (mean ± standard deviation) for the younger participants and 0.81 ± 0.42 degree/sec for older participants. Discrimination thresholds in younger and older adults were 4.83 ± 1.80 degree/sec and 4.33 ± 1.57 degree/sec, respectively. There was no difference in either measure between age groups. Perceptual thresholds were independent of the gain and phase of the VOR. CONCLUSIONS:: These results indicate that there is no inevitable loss of vestibular perception with aging. Elevated thresholds among the elderly are therefore suggestive of pathology rather than normal consequences of aging. Furthermore, perceptual thresholds offer additional insight, beyond that supplied by the VOR alone, into vestibular function. © 2014 by Lippincott Williams & Wilkins.


Author Keywords
Aging;  Detection;  Discrimination;  Psychometric;  Threshold;  Vestibular;  Vestibulo-ocular reflex


Document Type: Article
Source: Scopus

 

September 2, 2014

Logue, M.W.a b , Schu, M.a , Vardarajan, B.N.a , Farrell, J.a , Bennett, D.A.c , Buxbaum, J.D.d , Byrd, G.S.e , Ertekin-Taner, N.f , Evans, D.g , Foroud, T.h , Goate, A.i , Graff-Radford, N.R.f , Kamboh, M.I.j , Kukull, W.A.k , Manly, J.J.l
Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans
(2014) Alzheimer's and Dementia, . Article in Press. 


a Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA
b Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
c Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
d Departments of Neuroscience and Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA
e Department of Biology, North Carolina A and T State University, Greensboro, NC, USA
f Departments of Neuroscience and Neurology, Mayo Clinic, Jacksonville, FL, USA
g Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA
h Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA
i Department of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, MI, USA
j Department of Human Genetics and Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA, USA
k National Alzheimer's Coordinating Center and Department of Epidemiology, University of Washington, Seattle, WA, USA
l Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA


Abstract
Background: Less is known about the genetic basis of Alzheimer's disease (AD) in African Americans (AAs) than in non-Hispanic whites. Methods: Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD-related variants from WES was assessed in an AA discovery cohort of 422 cases and 394 controls. Replication was sought in an AA sample of 1037 cases and 1869 controls from the Alzheimer Disease Genetics Consortium (ADGC). Results: Forty-four single nucleotide polymorphisms (SNPs) from WES passed filtering criteria and were successfully genotyped. Nominally significant (P < .05) association to AD was observed with two African-descent specific AKAP9 SNPs in tight linkage disequilibrium: rs144662445 (P = .014) and rs149979685 (P = .037). These associations were replicated in the ADGC sample (rs144662445: P = .0022, odds ratio [OR] = 2.75; rs149979685: P = .0022, OR = 3.61). Conclusions: Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism. © 2014 The Alzheimer's Association.


Author Keywords
African American;  AKAP9;  Genetic association;  Late-onset Alzheimer's disease;  Rare variant;  Whole-exome sequencing


Document Type: Article in Press
Source: Scopus

Tu, T.-W.a , Budde, M.D.b , Xie, M.c , Chen, Y.-J.d , Wang, Q.e , Quirk, J.D.c , Song, S.-K.e
Phase-aligned multiple spin-echo averaging: a simple way to improve signal-to-noise ratio of in vivo mouse spinal cord diffusion tensor image
(2014) Magnetic Resonance Imaging, . Article in Press. 


a Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
b Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA
c Department of Pathology and Immunology, Washington University, St. Louis, MO, USA
d Department of Chemistry, Washington University, St. Louis, MO, USA
e Department of Radiology, Washington University, St. Louis, MO, USA


Abstract
Purpose: To improve signal-noise-ratio of in vivo mouse spinal cord diffusion tensor imaging using-phase aligned multiple spin-echo technique. Material and methods: In vivo mouse spinal cord diffusion tensor imaging maps generated by multiple spin-echo and conventional spin-echo diffusion weighting were examined to demonstrate the efficacy of multiple spin-echo diffusion sequence to improve image quality and throughput. Effects of signal averaging using complex, magnitude and phased images from multiple spin-echo diffusion weighting were also assessed. Bayesian probability theory was used to generate phased images by moving the coherent signals to the real channel to eliminate the effect of phase variation between echoes while preserving the Gaussian noise distribution. Signal averaging of phased multiple spin-echo images potentially solves both the phase incoherence problem and the bias of the elevated Rician noise distribution in magnitude image. The proposed signal averaging with Bayesian phase-aligned multiple spin-echo images approach was compared to the conventional spin-echo data acquired with doubling the scan time. The diffusion tensor imaging parameters were compared in the mouse contusion spinal cord injury. Significance level (p-value) and effect size (Cohen's d) were reported between the control and contused spinal cord to inspect the sensitivity of each approach in detecting white matter pathology. Results: Compared to the spin-echo image, the signal-noise-ratio increased to 1.84-fold using the phased image averaging and to 1.30-fold using magnitude image averaging in the spinal cord white matter. Multiple spin-echo phased image averaging showed improved image quality of the mouse spinal cord among the tested methods. Diffusion tensor imaging metrics obtained from multiple spin-echo phased images using three echoes and two averages closely agreed with those derived by spin-echo magnitude data with four averages (two times more in acquisition time). The phased image averaging correctly reflected pathological features in contusion spinal cord injury. Conclusion: Our in vivo imaging results indicate that averaging the phased multiple spin-echo images yields an 84% signal-noise-ratio increase over the spin-echo images and a 41% gain over the magnitude averaged multiple spin-echo images with equal acquisition time. Current results from the animal model of spinal cord injury suggest that the phased multiple spin-echo images could be used to improve signal-noise-ratio. © 2014.


Author Keywords
Bayesian phasing analysis;  DTI;  Multiple spin-echo;  Spinal cord


Document Type: Article in Press
Source: Scopus

Wang, J.-S.a , Nymark, S.c d , Frederiksen, R.c , Estevez, M.E.c e , Shen, S.Q.b , Corbo, J.C.b , Cornwall, M.C.c , Kefalov, V.J.a
Chromophore supply rate-limits mammalian photoreceptor dark adaptation
(2014) Journal of Neuroscience, 34 (34), pp. 11212-11221. 


a Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
b Departments of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Departments of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, United States
d Department of Electronics and Communications Engineering, Tampere University of Technology, BioMediTech, FI-33014 Tampere, Finland
e Department of Neuroscience, Brown University, Providence, RI 02912, United States


Abstract
Efficient regeneration of visual pigment following its destruction by light is critical for the function of mammalian photoreceptors. Here, we show that misexpression of a subset of cone genes in the rd7 mouse hybrid rods enables them to access the normally cone-specific retina visual cycle. The rapid supply of chromophore by the retina visual cycle dramatically accelerated the mouse rod dark adaptation. At the same time, the competition between rods and cones for retina-derived chromophore slowed cone dark adaptation, indicating that the cone specificity of the retina visual cycle is key for rapid cone dark adaptation. Our findings demonstrate that mammalian photoreceptor dark adaptation is dominated by the supply of chromophore. Misexpression of cone genes in rods may represent a novel approach to treating visual disorders associated with mutations of visual cycle proteins or with reduced retinal pigment epithelium function due to aging. © 2014 the authors.


Author Keywords
Dark adaptation;  Photoreceptors;  Pigment regeneration;  Retina;  Retinol dehydrogenase;  Visual cycle


Document Type: Article
Source: Scopus

Qureshi, A.Y.a b , Mueller, S.d e , Snyder, A.Z.f , Mukherjee, P.g , Berman, J.I.i , Roberts, T.P.L.i , Nagarajan, S.S.g , Spiro, J.E.j , Chung, W.K.k , Sherr, E.H.h , Buckner, R.L.a c d
Opposing brain differences in 16p11.2 deletion and duplication carriers
(2014) Journal of Neuroscience, 34 (34), pp. 11199-11211. 


a Harvard University, Department of Psychology and Center for Brain Science, Cambridge, MA 02138, United States
b Departments of Neurology, Massachusetts General Hospital, Boston, MA 02114, United States
c Departments of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, United States
d Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, United States
e Ludwig Maximilians University Munich, Institute of Clinical Radiology, Munich 81377, Germany
f Departments of Neurology and Radiology, Washington University School of Medicine in St Louis, St Louis, MO 63110, United States
g Departments of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, United States
h Departments of Neurology, University of California, San Francisco, CA 94158, United States
i Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States
j Simons Foundation, New York, NY 10010, United States
k Department of Pediatrics and Medicine, Columbia University Medical Center, New York, NY 10032, United States


Abstract
Deletions and duplications of the recurrent ~600 kb chromosomal BP4-BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development. © 2014 the authors.


Author Keywords
16p11.2;  ASD;  CNV;  Copy number variation;  Morphometry;  Structural MRI


Document Type: Article
Source: Scopus

Doyle, W.I.a , Hammen, G.F.b , Meeks, J.P.a
Ex vivo preparations of the intact vomeronasal organ and accessory olfactory bulb
(2014) Journal of Visualized Experiments, (90), art. no. e51813, . 


a Department of Neuroscience, UT Southwestern Medical Center, United States
b Department of Anatomy and Neurobiology, Washington University in St. Louis, United States


Abstract
The mouse accessory olfactory system (AOS) is a specialized sensory pathway for detecting nonvolatile social odors, pheromones, and kairomones. The first neural circuit in the AOS pathway, called the accessory olfactory bulb (AOB), plays an important role in establishing sex-typical behaviors such as territorial aggression and mating. This small (&lt;1 mm3) circuit possesses the capacity to distinguish unique behavioral states, such as sex, strain, and stress from chemosensory cues in the secretions and excretions of conspecifics. While the compact organization of this system presents unique opportunities for recording from large portions of the circuit simultaneously, investigation of sensory processing in the AOB remains challenging, largely due to its experimentally disadvantageous location in the brain. Here, we demonstrate a multi-stage dissection that removes the intact AOB inside a single hemisphere of the anterior mouse skull, leaving connections to both the peripheral vomeronasal sensory neurons (VSNs) and local neuronal circuitry intact. The procedure exposes the AOB surface to direct visual inspection, facilitating electrophysiological and optical recordings from AOB circuit elements in the absence of anesthetics. Upon inserting a thin cannula into the vomeronasal organ (VNO), which houses the VSNs, one can directly expose the periphery to social odors and pheromones while recording downstream activity in the AOB. This procedure enables controlled inquiries into AOS information processing, which can shed light on mechanisms linking pheromone exposure to changes in behavior.


Author Keywords
Accessory olfactory bulb;  Ex vivo;  Issue 90;  Mouse;  Neuroscience;  Olfaction;  Vomeronasal organ


Document Type: Article
Source: Scopus

Calarge, C.A.a , Nicol, G.b , Schlechte, J.A.c , Burns, T.L.d
Cardiometabolic outcomes in children and adolescents following discontinuation of long-term risperidone treatment
(2014) Journal of Child and Adolescent Psychopharmacology, 24 (3), pp. 120-129. 


a Department of Psychiatry Pediatrics, University of Iowa Carver College of Medicine, 500 Newton Road, Iowa City, IA 52242, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
d University of Iowa College of Public Health, Iowa City, IA, United States


Abstract
Objective: Second-generation antipsychotics (SGAs) cause weight gain and cardiometabolic abnormalities in children and adolescents. Less well-investigated is the outcome of these adverse events following SGA discontinuation, which we examined. Methods: Medically healthy 7 to 17-year-old patients treated with risperidone for ≥6 months were enrolled and returned for follow-up, 1.5 years later. Treatment history was extracted from the medical and pharmacy records. Anthropometric and laboratory measurements were obtained at each research visit. Multivariable linear regression analysis and Fisher's exact test were used to compare participants who remained on risperidone at follow-up (Risp Cont Group) with those who had discontinued SGA treatment (SGA Disc Group) and those who had switched to another SGA (SGA Cont Group). Correlational analyses examined the association between change in age-sex specific body mass index (BMI) z score between study entry and follow-up and change in cardiometabolic outcomes. Results: The sample consisted of 101 participants (93% male) with a mean age of 11.7±2.6 years at study entry. The majority had an externalizing disorder and received 0.03±0.02mg/kg/ day of risperidone, for 2.5±1.6 years. At follow-up, 18% (n=18) were in the SGA Disc Group and 9% (n=9) were in the SGA Cont Group. BMI z score decreased in the SGA Disc Group, remained unchanged in the Risp Cont Group (n=74), and increased in the SGA Cont Group. Importantly, the change in BMI z score between study entry and follow-up was significantly correlated with the change in systolic and diastolic blood pressure z scores, heart rate, waist circumference, percent body fat, inflammatory markers, fasting total insulin, homeostatic model assessment insulin resistance index (HOMA-IR), C-peptide, total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, triglycerides, triglycerides/HDL ratio, and leptin. Conclusions: Following several years of treatment, risperidone discontinuation is associated with a reversal of the excessive weight gain, mediated by a negative energy balance, and a corresponding improvement in cardiometabolic parameters. © 2014, Mary Ann Liebert, Inc.


Document Type: Article
Source: Scopus

Morrow-Howell, N.a b , Putnam, M.c , Lee, Y.S.d , Greenfield, J.C.e , Inoue, M.f , Chen, H.a
An investigation of activity profiles of older adults
(2014) Journals of Gerontology - Series B Psychological Sciences and Social Sciences, 69 (5), pp. 809-821. 


a Brown School of Social Work, Washington University in St Louis, Campus Box 1196, St Louis, MO 63130, United States
b Center for Aging, Washington University in St Louis, Missouri, United States
c School of Social Work, Simmons College, Boston, MA, United States
d Department of Social Welfare, Incheon National University, Yeonsu-gu, Incheon, South Korea
e Graduate School of Social Work, University of Denver, Colorado, United States
f Graduate School of Social Work, Boston College, Chestnut Hill, MA, United States


Abstract
Objectives. In this study, we advance knowledge about activity engagement by considering many activities simultaneously to identify profiles of activity among older adults. Further, we use cross-sectional data to explore factors associated with activity profiles and prospective data to explore activity profiles and well-being outcomes. Method. We used the core survey data from the years 2008 and 2010, as well as the 2009 Health and Retirement Study Consumption and Activities Mail Survey (HRS CAMS). The HRS CAMS includes information on types and amounts of activities. We used factor analysis and latent class analysis to identify activity profiles and regression analyses to assess antecedents and outcomes associated with activity profiles. Results. We identified 5 activity profiles: Low Activity, Moderate Activity, High Activity, Working, and Physically Active. These profiles varied in amount and type of activities. Demographic and health factors were related to profiles. Activity profiles were subsequently associated with self-rated health and depression symptoms. Discussion. The use of a 5-level categorical activity profile variable may allow more complex analyses of activity that capture the "whole person." There is clearly a vulnerable group of low-activity individuals as well as a High Activity group that may represent the "active ageing" vision. © The Author 2014.


Author Keywords
Activity;  Activity patterns;  Engagement;  Time use


Document Type: Article
Source: Scopus

Cavazos-Rehg, P., Krauss, M., Grucza, R., Bierut, L.
Characterizing the followers and tweets of a marijuana-focused twitter handle
(2014) Journal of Medical Internet Research, 16 (6), art. no. e157, . 


Washington University, School of Medicine, 660 South Euclid, St. Louis, MO, United Kingdom


Abstract
Twitter is a popular social media forum for sharing personal experiences, interests, and opinions. An improved understanding of the discourse on Twitter that encourages marijuana use can be helpful for tailoring and targeting online and offline prevention messages. Objectives: The intent of the study was to assess the content of tweets and the demographics of followers of a popular pro-marijuana Twitter handle (@stillblazingtho). Methods: We assessed the sentiment and content of tweets (sent from May 1 to December 31, 2013), as well as the demographics of consumers that follow a popular pro-marijuana Twitter handle (approximately 1,000,000 followers) using Twitter analytics from Demographics Pro. This analytics company estimates demographic characteristics based on Twitter behavior/usage, relying on multiple data signals from networks, consumption, and language and requires confidence of 95% or above to make an estimate of a single demographic characteristic. Results: A total of 2590 tweets were sent from @stillblazingtho during the 8-month period and 305 (11.78%) replies to another Twitter user were excluded for qualitative analysis. Of the remaining 2285 tweets, 1875 (82.06%) were positive about marijuana, 403 (17.64%) were neutral, and 7 (0.31%) appeared negative about marijuana. Approximately 1101 (58.72%) of the positive marijuana tweets were perceived as jokes or humorous, 340 (18.13%) implied that marijuana helps you to feel good or relax, 294 (15.68%) mentioned routine, frequent, or heavy use, 193 (10.29%) mentioned blunts, marijuana edibles, or paraphernalia (eg, bongs, vaporizers), and 186 (9.92%) mentioned other risky health behaviors (eg, tobacco, alcohol, other drugs, sex). The majority (699,103/959,143; 72.89%) of @stillblazingtho followers were 19 years old or younger. Among people ages 17 to 19 years, @stillblazingtho was in the top 10% of all Twitter handles followed. More followers of @stillblazingtho in the United States were African American (323,107/759,407; 42.55%) or Hispanic (90,732/759,407; 11.95%) than the Twitter median average (African American 22.4%, inter-quartile ratio [IQR] 5.1-62.5%; Hispanic 5.4%, IQR 3.0-10.8%) and among Hispanics, @stillblazingtho was in the top 30% of all Twitter handles followed. Conclusions: Young people are especially responsive to social media influences and often establish substance use patterns during this phase of development. Our findings underscore the need for surveillance efforts to monitor the pro-marijuana content reaching young people on Twitter.


Author Keywords
Marijuana;  Social media;  Twitter


Document Type: Article
Source: Scopus

Barcroft, J., Sommers, M.S.
Effects of variability in fundamental frequency on L2 vocabulary learning : A comparison between learners who do and do not speak a tone language
(2014) Studies in Second Language Acquisition, 36 (3), pp. 423-449. 


Washington University in St. Louis, Department of Romance Languages and Literatures, One Brookings Drive, St. Louis, MO 63130-4899, United States


Abstract
Previous studies (Barcroft & Sommers, 2005; Sommers & Barcroft, 2007) have demonstrated that variability in talker, speaking style, and speaking rate positively affect second language vocabulary learning, whereas variability in overall amplitude and fundamental frequency (F0) do not, at least for native English speakers. Sommers and Barcroft (2007) hypothesized that English speakers do not benefit (with regard to second language vocabulary learning) from amplitude and F0 variability because these are not phonetically relevant to them. The present study further tested this hypothesis by examining effects of F0 variability among adults who speak a tone language (Zapotec-Spanish bilinguals) and those who do not speak a tone language (Spanish speakers with substantial knowledge of English). Participants attempted to learn 24 Russian words while hearing the words and viewing their corresponding pictures. Three levels of F0 variability were compared. Fundamental frequency variability significantly improved vocabulary learning for speakers of the tone language (Zapotec) but not for the Spanish speakers. This result provides strong evidence that effects of acoustic variability on learning new word forms depend on phonetic relevance. © Cambridge University Press 2013.


Document Type: Article
Source: Scopus

Holtzman, N.S.a , Senne, A.L.b
Fast and Slow Sexual Strategies Are Not Opposites: Implications for Personality and Psychopathology
(2014) Psychological Inquiry, 25 (3-4), pp. 337-340. 


a Department of Psychology, Georgia Southern University, Statesboro, GA, United States
b Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States


Document Type: Note
Source: Scopus

Chung, H., Chapman, W.C.
Liver transplantation for metastatic neuroendocrine tumors
(2014) Advances in Surgery, 48 (1), pp. 235-252. 


Department of General Surgery, Washington University in St Louis, Campus Box 8109, 660 South Euclid Avenue, St Louis, MO 63110, United States


Author Keywords
Carcinoid;  Islet cell tumors;  Liver metastases;  Liver transplantation for malignancy;  Neuroendocrine tumors


Document Type: Review
Source: Scopus

Ortega, M.a , Ances, B.M.a b c d e
Role of HIV in amyloid metabolism
(2014) Journal of Neuroimmune Pharmacology, 9 (4), pp. 483-491. 


a Department of Neurology, School of Medicine, Washington University in St. Louis, Box 8111, 660 South Euclid Ave, Saint Louis, MO 63110, United States
b Department of Radiology, Washington University in St. Louis, Box 8111, 660 South Euclid Ave, Saint Louis, MO 63110, United States
c Department of Biomedical Engineering, Washington University in St. Louis, Box 8111, 660 South Euclid Ave, Saint Louis, MO 63110, United States
d Department of Microbiology, Washington University in St. Louis, Box 8111, 660 South Euclid Ave, Saint Louis, MO 63110, United States
e Hope Center for Neurological Disorders, Washington University in St. Louis, Box 8111, 660 South Euclid Ave, Saint Louis, MO 63110, United States


Abstract
HIV infection has changed from an acute devastating disease to a more chronic illness due to combination anti-retroviral treatment (cART). In the cART era, the life expectancy of HIV-infected (HIV+) individuals has increased. More HIV+individuals are aging with current projections suggesting that 50 % of HIV+individuals will be over 50 years old by 2015. With advancing age, HIV+individuals may be at increased risk of developing other potential neurodegenerative disorders [especially Alzheimer's disease (AD)]. Pathology studies have shown that HIV increases intra and possibly extracellular amyloid beta (Aβ42), a hallmark of AD. We review the synthesis and clearance of Aβ42; the effects of HIV on the amyloid pathway; and contrast the impact of AD and HIV on Aβ42 metabolism. Biomarker studies (cerebrospinal fluid AB and amyloid imaging) in HIV+participants have shown mixed results. CSF Aβ42 has been shown to be either normal or diminished in with HIV associated neurocognitive disorders (HAND). Amyloid imaging using [11C] PiB has also not demonstrated increased extracellular amyloid fibrillar deposits in HAND. We further demonstrate that Aβ42 deposition is not increased in older HIV+participants using [11C] PiB amyloid imaging. Together, these results suggest that HIV and aging each independently affect Aβ42 deposition with no significant interaction present. Older HIV+individuals are probably not at increased risk for developing AD. However, future longitudinal studies of older HIV+individuals using multiple modalities (including the combination of CSF markers and amyloid imaging) are necessary for investigating the effects of HIV on Aβ42 metabolism. © 2014 Springer Science+Business Media.


Author Keywords
Amyloid;  Amyloid imaging;  Cerebrospinal fluid (CSF);  CNS;  Combination anti-retroviral therapy (cART);  HIV;  HIV associated neurocognitive disorders (HAND)


Document Type: Review
Source: Scopus

Pettus-Davis, C.
Social support among releasing men prisoners with lifetime trauma experiences
(2014) International Journal of Law and Psychiatry, 37 (5), pp. 512-523. 


Washington University in St. Louis, Brown School of Social Work, Campus Box 1196, Goldfarb Hall, One Brookings Drive, St. Louis, MO 63130, United States


Abstract
High rates of lifetime trauma experiences exist among men incarcerated in US state and federal prisons. Because lifetime trauma experiences have been linked to problematic behavioral and psychiatric outcomes for incarcerated populations, trauma-informed interventions could improve post-release well-being of releasing men prisoners with trauma histories. Social support has consistently been found to have a positive impact on trauma-related outcomes in non-incarcerated populations. Therefore, it is reasonable to hypothesize that social support may be an important intervention component for releasing men prisoners with trauma experiences; yet, the relationship between trauma experiences, psychiatric and behavioral factors, and social support has received almost no attention in research with men prisoners. Using a probability sample of 165 soon-to-be-released men, the present study examined differences in certain demographic, criminal justice history, mental health, substance abuse, and social support (type, quality, amount, and source) variables between releasing men prisoners with and without lifetime trauma experiences. Results indicate that men with trauma histories had more negative social support experiences and fewer positive social support resources before prison than their counterparts. Men with trauma histories also had more lifetime experiences with mental health and substance use problems. On further investigation of the subsample of men with trauma histories, those who were older, had substance use disorders, and histories of mental health problems anticipated fewer post-release social support resources. Study findings underscore the nuances of social support for men prisoners with trauma experiences and point to implications for future directions in targeted trauma-informed intervention development for releasing men prisoners. © 2014 Elsevier Ltd.


Author Keywords
Intervention;  Men;  Prisoners;  Reintegration;  Social support;  Trauma


Document Type: Article
Source: Scopus

Xiang, C., Arends, J.J.A., Jacquin, M.F.
Whisker-related circuitry in the trigeminal nucleus principalis: Ultrastructure
(2014) Somatosensory and Motor Research, 31 (3), pp. 141-151. 


Department of Neurology, Washington University School of Medicine, Box 8111, St Louis, MO 63110, United States


Abstract
Trigeminal (V) nucleus principalis (PrV) is the requisite brainstem nucleus in the whisker-to-barrel cortex model system that is widely used to reveal mechanisms of map formation and information processing. Yet, little is known of the actual PrV circuitry. In the ventral "barrelette" portion of the adult mouse PrV, relationships between V primary afferent terminals, thalamic-projecting PrV neurons, and gamma-aminobutyric acid (GABA)-ergic terminals were analyzed in the electron microscope. Primary afferents, thalamic-projecting cells, and GABAergic terminals were labeled, respectively, by Neurobiotin injections in the V ganglion, horseradish peroxidase injections in the thalamus, and postembedding immunogold histochemistry. Primary afferent terminals (Neurobiotin- and glutamate-immunoreactive) display asymmetric and multiple synapses predominantly upon the distal dendrites and spines of PrV cells that project to the thalamus. Primary afferents also synapse upon GABAergic terminals. GABAergic terminals display symmetric synapses onto primary afferent terminals, the somata and dendrites (distal, mostly) of thalamic-projecting neurons, and GABAergic dendrites. Thus, primary afferent inputs through the PrV are subject to pre- and postsynaptic GABAergic influences. As such, circuitry exists in PrV "barrelettes" for primary afferents to directly activate thalamic-projecting and inhibitory local circuit cells. The latter are synaptically associated with themselves, the primary afferents, and with the thalamic-projecting neurons. Thus, whisker-related primary afferent inputs through PrV projection neurons are pre- and postsynaptically modulated by local circuits. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.


Author Keywords
Barrel;  GABA;  Glutamate;  Principal trigeminal nucleus;  Synapse;  Thalamus;  Vibrissa


Document Type: Article
Source: Scopus