“Incidence of uveitis and macular edema among patients taking fingolimod 0.5 mg for multiple sclerosis” (2020) Journal of Ophthalmic Inflammation and Infection
Incidence of uveitis and macular edema among patients taking fingolimod 0.5 mg for multiple sclerosis
(2020) Journal of Ophthalmic Inflammation and Infection, 10 (1), art. no. 24, .
Sonne, S.J.a , Smith, B.T.b c
a St. Louis University School of Medicine, St. Louis, United States
b The Retina Institute in St. Louis, 2201 S Brentwood Blvd, St. Louis, MO 63144, United States
c Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, United States
Abstract
Background: Patients with multiple sclerosis (MS) have a higher incidence of uveitis compared with the general population. Fingolimod, a first line disease modifying drug used in multiple sclerosis, may cause macular edema and thus requires ophthalmic examination. However, murine models and anecdotal reports suggest fingolimod may reduce the incidence of uveitis. Purpose: To report the incidence of uveitis and macular edema among those on fingolimod 0.5 mg (Gilenya®) therapy for multiple sclerosis (MS). Methods: Retrospective review of patients on fingolimod who developed uveitis and/or macular edema. Results: No patients had an occurrence or history of uveitis. Four of the 188 (2.13%) patients developed macular edema without ocular inflammation. One of the 188 (0.53%) patients developed Acute Macular Neuroretinopathy. Conclusion: Patients taking fingolimod have a lower incidence of uveitis than expected in a population of MS patients. © 2020, The Author(s).
Author Keywords
Acute macular neuroretinopathy; Cystoid macular edema; Fingolimod; Gilenya; Macular edema; Multiple sclerosis; Uveitis
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease” (2020) Scientific Reports
Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease
(2020) Scientific Reports, 10 (1), art. no. 15157, .
Nelvagal, H.R.a e , Hurtado, M.L.f , Eaton, S.L.f , Kline, R.A.f , Lamont, D.J.g , Sands, M.S.b d , Wishart, T.M.f , Cooper, J.D.a b c e
a Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University in St Louis, School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, United States
b Department of Genetics, Washington University in St Louis, School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, United States
c Department of Neurology, Washington University in St Louis, School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, United States
d Department of Medicine, Washington University in St Louis, School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, United States
e Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
f The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, United Kingdom
g FingerPrints Proteomics Facility, College of Life Sciences, University of Dundee, Dundee, United Kingdom
Abstract
CLN1 disease is a fatal inherited neurodegenerative lysosomal storage disease of early childhood, caused by mutations in the CLN1 gene, which encodes the enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology in Ppt1-deficient (Ppt1−/−) mice and human CLN1 disease that contributes to clinical outcome and precedes the onset of brain pathology. Here, we quantified this spinal pathology at 3 and 7 months of age revealing significant and progressive glial activation and vulnerability of spinal interneurons. Tandem mass tagged proteomic analysis of the spinal cord of Ppt1−/−and control mice at these timepoints revealed a significant neuroimmune response and changes in mitochondrial function, cell-signalling pathways and developmental processes. Comparing proteomic changes in the spinal cord and cortex at 3 months revealed many similarly affected processes, except the inflammatory response. These proteomic and pathological data from this largely unexplored region of the CNS may help explain the limited success of previous brain-directed therapies. These data also fundamentally change our understanding of the progressive, site-specific nature of CLN1 disease pathogenesis, and highlight the importance of the neuroimmune response. This should greatly impact our approach to the timing and targeting of future therapeutic trials for this and similar disorders. © 2020, The Author(s).
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Neurological correlates of brain reward circuitry linked to opioid use disorder (OUD): Do homo sapiens acquire or have a reward deficiency syndrome?” (2020) Journal of the Neurological Sciences
Neurological correlates of brain reward circuitry linked to opioid use disorder (OUD): Do homo sapiens acquire or have a reward deficiency syndrome?
(2020) Journal of the Neurological Sciences, 418, art. no. 117137, .
Gold, M.S.a , Baron, D.b , Bowirrat, A.c , Blum, K.b
a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Graduate School of Biomedical Sciences, Western University Health Sciences, Pomona, CA, United States
c Department of Neuroscience and Genetics, Interdisciplinary Center Herzliya, Israel
Abstract
The extant literature confirms that an array of polymorphic genes related to- neurotransmitters and second messengers govern the net release of dopamine in the Nucleus Accumbens (NAc) in the mesolimbic region of the brain. They are linked predominantly to motivation, anti-stress, incentive salience (wanting), and wellbeing. Notably, in 2000 the Nobel Prize was awarded to Carlsson, Greengard, and Kandel for their work on the molecular and cellular function of dopaminergic activity at neurons. This historical psychopharmacological work involved neurotransmission of serotonin, endorphins, glutamate, and dopamine, and the seminal work of Blum, Gold, Volkow, Nestler, and others related to neurotransmitter function and related behaviors. Currently, Americans are facing their second and worst opioid epidemic, prescribed opioids, and easy access drive this epidemic of overdoses, and opioid use disorders (OUDs). Presently the clinical consensus is to treat OUD, as if it were an opioid deficiency syndrome, with long-term to life-long opioid substitution therapy. Opioid agonist administration is seen as necessary to replace missing opioids, treat OUD, and prevent overdoses, like insulin is used to treat diabetes. Treatment of OUD and addiction, in general, is similar to the endocrinopathy conceptualization in that it views opioid agonist MATs as an essential core to therapy. Is this approach logical? Other than as harm reduction, is using opioids to treat OUD therapeutic or harmful in the long term? This historical Trieste provides a molecular framework to understand the current underpinnings of endorphinergic/dopaminergic mechanisms related to opioid deficiency syndrome and generalized reward processing depletion. WC 249. © 2020 Elsevier B.V.
Author Keywords
Brain reward Cascade (BRC); Dopamine deficiency syndrome; Dopamine release and homeostasis; Endorphinergic deficiency syndrome; Endorphinergic mechanisms; Genetic testing of addiction liability; Neurotransmission; Opioid use disorder (OUD); Precision addiction management’; Reward deficiency syndrome (RDS)
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Interactions between knockout of schizophrenia risk factor Dysbindin-1 and copper metabolism in mice” (2020) Brain Research Bulletin
Interactions between knockout of schizophrenia risk factor Dysbindin-1 and copper metabolism in mice
(2020) Brain Research Bulletin, 164, pp. 339-349.
Schoonover, K.E.a , McMeekin, L.J.b , Farmer, C.B.c , Varghese, N.E.c , Queern, S.L.d e , Lapi, S.E.d e , Cowell, R.M.b , Roberts, R.C.c
a Department of Psychology and Behavioral Neuroscience, University of Alabama at Birmingham, United States
b Department of Neuroscience, Southern Research Institute, United States
c Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, United States
d Department of Radiology, University of Alabama at Birmingham, United States
e Department of Chemistry, Washington University in St. Louis, United States
Abstract
Background and Purpose: DTNBP1 gene variation and lower dysbindin-1 protein are associated with schizophrenia. Previous evidence suggests that downregulated dysbindin-1 expression results in lower expression of copper transporters ATP7A (intracellular copper transporter) and SLC31A1 (CTR1; extracellular copper transporter), which are required for copper transport across the blood brain barrier. However, whether antipsychotic medications used for schizophrenia treatment may modulate these systems is unclear. Experimental Approach: The current study measured behavioral indices of neurological function in dysbindin-1 functional knockout (KO) mice and their wild-type (WT) littermates with or without quetiapine treatment. We assessed serum and brain copper levels, ATP7A and CTR1 mRNA, and copper transporter-expressing cellular population transcripts: TTR (transthyretin; choroid plexus epithelial cells), MBP (myelin basic protein; oligodendrocytes), and GJA1 (gap-junction protein alpha-1; astrocytes) in cortex and hippocampus. Key Results: Regardless of genotype, quetiapine significantly reduced TTR, MBP, CTR1 mRNA, and serum copper levels. Neurological function of untreated KO mice was abnormal, and ledge instability was rescued with quetiapine. KO mice were hyperactive after 10 min in the open-field assay, which was not affected by treatment. Conclusions and Implications: Dysbindin-1 KO results in hyperactivity, altered serum copper, and neurological impairment, the last of which is selectively rescued with quetiapine. Antipsychotic treatment modulates specific cellular populations, affecting myelin, the choroid plexus, and copper transport across the blood brain barrier. Together these results indicate the widespread impact of antipsychotic treatment, and that alteration of dysbindin-1 may be sufficient, but not necessary, for specific schizophrenia pathology. © 2020 Elsevier Inc.
Author Keywords
ATP7A; Copper; CTR1; Dysbindin; Quetiapine; Schizophrenia; Seroquel
Document Type: Article
Publication Stage: Final
Source: Scopus
“A Novel Surgical Technique for the Management of Cerebrospinal Fluid Gusher Encountered During Cochlear Implantation” (2020) Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society (and) European Academy of Otology and Neurotology
A Novel Surgical Technique for the Management of Cerebrospinal Fluid Gusher Encountered During Cochlear Implantation
(2020) Otology & neurotology: Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 41 (9), p. e1177.
Tolisano, A.M.a , Wick, C.C.b , Kutz, J.W., Jrc
a Department of Otolaryngology-Head and Neck Surgery, Walter Reed National Military Medical Center, Bethesda, MD, United States
b Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States
c Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, TX, United States
Abstract
: Cerebrospinal fluid (CSF) gusher encountered during cochlear implantation are most commonly encountered in the setting of an inner ear abnormality. Repair of the gusher is essential to prevent CSF egress postoperatively and to decrease the risk of meningitis. Various methods to repair a CSF gusher have been described, including tight packing of the cochleostomy with fascia, lumbar drainage, and Eustachian tube packing with ear canal overclosure. We describe a novel and simple technique using a fascia ring placed around the cochlear implantation electrode (Cochlear Corporation, CI522) as a means to treat CSF gusher. The fascia is slid down the electrode after insertion, allowing circumferential coverage of the defect. The following video will provide an overview of patients at risk for CSF gusher and demonstrate the technique described above.SDC video link: http://links.lww.com/MAO/B52.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Cochlear Implant Outcomes Following Vestibular Schwannoma Resection: Systematic Review” (2020) Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society (and) European Academy of Otology and Neurotology
Cochlear Implant Outcomes Following Vestibular Schwannoma Resection: Systematic Review
(2020) Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 41 (9), pp. 1190-1197.
Wick, C.C.a , Butler, M.J.b , Yeager, L.H.c , Kallogjeri, D.a , Durakovic, N.a , McJunkin, J.L.a , Shew, M.A.a , Herzog, J.A.a , Buchman, C.A.a
a Department of Otolaryngology-Head and Neck Surgery
b Program in Audiology and Communication Sciences, Department of Otolaryngology-Head and Neck Surgery
c Library Services, Washington University School of Medicine, St. Louis, MO, United States
Abstract
OBJECTIVE: Hearing loss remains a significant morbidity for patients with vestibular schwannomas (VS). A growing number of reports suggest audibility with cochlear implantation following VS resection; however, there is little consensus on preferred timing and cochlear implant (CI) performance. DATA SOURCES: A systematic literature search of the Ovid Medline, Embase, Scopus, and clinicaltrails.gov databases was performed on 9/7/2018. PRISMA reporting guidelines were followed. STUDY SELECTION: Included studies reported CI outcomes in an ear that underwent a VS resection. Untreated VSs, radiated VSs, and CIs in the contralateral ear were excluded. DATA EXTRACTION: Primary outcomes were daily CI use and attainment of open-set speech. Baseline tumor and patient characteristics were recorded. Subjects were divided into two groups: simultaneous CI placement with VS resection (Group 1) versus delayed CI placement after VS resection (Group 2). DATA SYNTHESIS: Twenty-nine articles with 93 patients met inclusion criteria. Most studies were poor quality due to their small, retrospective design. Group 1 had 46 patients, of whom 80.4% used their CI on a daily basis and 50.0% achieved open-set speech. Group 2 had 47 patients, of whom 87.2% used their CI on a daily basis and 59.6% achieved open-set speech. Group 2 had more NF2 patients and larger tumors. CI timing did not significantly impact outcomes. CONCLUSIONS: Audibility with CI after VS resection is feasible. Timing of CI placement (simultaneous versus delayed) did not significantly affect performance. Overall, 83.9% used their CI on a daily basis and 54.8% achieved open-set speech.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Feeding specialization and longer generation time are associated with relatively larger brains in bees” (2020) Proceedings. Biological Sciences
Feeding specialization and longer generation time are associated with relatively larger brains in bees
(2020) Proceedings. Biological Sciences, 287 (1935), p. 20200762.
Sayol, F.a b c , Collado, M.Á.d , Garcia-Porta, J.e , Seid, M.A.f , Gibbs, J.g , Agorreta, A.h , Mauro, D.S.h , Raemakers, I.i , Sol, D.j k , Bartomeus, I.d
a Department of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden
b Gothenburg Global Biodiversity Centre, Gothenburg, Sweden
c Centre for Biodiversity and Environment Research, Department of Genetics, Evolution and Environment, University College London, London, United Kingdom
d Estación Biológica de Doñana (EBD-CSIC), Avda. Américo Vespucio 26 ,Isla de la Cartuja, Sevilla, 41092, Spain
e Department of Biology, Washington University in St. Louis, St. Louis, United States
f Biology Department, Neuroscience Program, University of Scranton, Scranton, United States
g Department of Entomology, University of Manitoba, Winnipeg, MB, Canada
h Department of Biodiversity, Ecology, Evolution, Complutense University of MadridMadrid 28040, Spain
i Van Caldenborghstraat 26, 6247CG, The Netherlands, Netherlands
j CREAF, Cerdanyola del Vallès, Catalonia, Spain
k CSIC, Cerdanyola del Vallès, Catalonia, Spain
Abstract
Despite their miniature brains, insects exhibit substantial variation in brain size. Although the functional significance of this variation is increasingly recognized, research on whether differences in insect brain sizes are mainly the result of constraints or selective pressures has hardly been performed. Here, we address this gap by combining prospective and retrospective phylogenetic-based analyses of brain size for a major insect group, bees (superfamily Apoidea). Using a brain dataset of 93 species from North America and Europe, we found that body size was the single best predictor of brain size in bees. However, the analyses also revealed that substantial variation in brain size remained even when adjusting for body size. We consequently asked whether such variation in relative brain size might be explained by adaptive hypotheses. We found that ecologically specialized species with single generations have larger brains-relative to their body size-than generalist or multi-generation species, but we did not find an effect of sociality on relative brain size. Phylogenetic reconstruction further supported the existence of different adaptive optima for relative brain size in lineages differing in feeding specialization and reproductive strategy. Our findings shed new light on the evolution of the insect brain, highlighting the importance of ecological pressures over social factors and suggesting that these pressures are different from those previously found to influence brain evolution in other taxa.
Author Keywords
Apoidea; brain evolution; lecticity; voltinism
Document Type: Article
Publication Stage: Final
Source: Scopus
“Axon Regeneration in the Mammalian Optic Nerve” (2020) Annual Review of Vision Science
Axon Regeneration in the Mammalian Optic Nerve
(2020) Annual Review of Vision Science, 6, pp. 195-213.
Williams, P.R.a , Benowitz, L.I.b c d e , Goldberg, J.L.f , He, Z.e g h
a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
b Laboratories for Neuroscience Research in Neurosurgery, Boston Children’s Hospital, Boston, MA 02115, United States
c F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Boston, Massachusetts 02115, USA; email: zhigang.he@childrens.harvard.edu
d Department of Neurosurgery, Harvard Medical School, Boston, MA 02115, United States
e Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, United States
f Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Palo Alto, CA 94303, United States
g F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Boston, Massachusetts 02115, USA; email:
h Department of Neurology, Harvard Medical School, Boston, MA 02115, United States
Abstract
The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.
Author Keywords
axon regeneration; KLF; mTOR; oncomodulin; retinal ganglion cells; survival
Document Type: Article
Publication Stage: Final
Source: Scopus
“Association of education with Aβ burden in preclinical familial and sporadic Alzheimer disease” (2020) Neurology
Association of education with Aβ burden in preclinical familial and sporadic Alzheimer disease
(2020) Neurology, 95 (11), pp. e1554-e1564.
Gonneaud, J.a , Bedetti, C.b , Pichet Binette, A.b , Benzinger, T.L.S.b , Morris, J.C.b , Bateman, R.J.b , Poirier, J.b , Breitner, J.C.S.b , Villeneuve, S.c , DIAN Study Group and the PREVENT-AD Research Groupd
a From the Department of Psychiatry (J.G., C.B., A.P.B., J.P., J.C.S.B., S.V.), McGill University; Douglas Mental Health University Institute (J.G., C.B., A.P.B., J.P., J.C.S.B., S.V.), StoP-AD Centre, Montreal, Canada; Knight Alzheimer’s Disease Research Center (T.L.S.B., J.C.M., R.J.B.); and Washington University School of Medicine (T.L.S.B., J.C.M., R.J.B.), St. Louis, MO. sylvia.villeneuve@mcgill.ca julie.gonneaud@mail.mcgill.ca
b From the Department of Psychiatry (J.G., C.B., A.P.B., J.P., J.C.S.B., S.V.), McGill University; Douglas Mental Health University Institute (J.G., C.B., A.P.B., J.P., J.C.S.B., S.V.), StoP-AD Centre, Montreal, Canada; Knight Alzheimer’s Disease Research Center (T.L.S.B., J.C.M., R.J.B.); and Washington University School of Medicine (T.L.S.B., J.C.M., R.J.B.), St. Louis, MO
c From the Department of Psychiatry (J.G., C.B., A.P.B., J.P., J.C.S.B., S.V.), McGill University; Douglas Mental Health University Institute (J.G., C.B., A.P.B., J.P., J.C.S.B., S.V.), StoP-AD Centre, Montreal, Canada; Knight Alzheimer’s Disease Research Center (T.L.S.B., J.C.M., R.J.B.); and Washington University School of Medicine (T.L.S.B., J.C.M., R.J.B.), St. Louis, MO. julie.gonneaud@mail.mcgill.ca
Abstract
OBJECTIVE: To determine whether years of education and the ε4 risk allele at APOE influence β-amyloid (Aβ) pathology similarly in asymptomatic individuals with a family history of sporadic Alzheimer disease (AD) and presymptomatic autosomal dominant AD mutation carriers. METHODS: We analyzed cross-sectional data from 106 asymptomatic individuals with a parental history of sporadic AD (PREVENT-AD cohort; age 67.28 ± 4.72 years) and 117 presymptomatic autosomal dominant AD mutation carriers (DIAN cohort; age 35.04 ± 9.43 years). All participants underwent structural MRI and Aβ-PET imaging. In each cohort we investigated the influence of years of education, APOE ε4 status, and their interaction on Aβ-PET. RESULTS: Asymptomatic individuals with a parental history of sporadic AD showed increased Aβ burden associated with APOE ε4 carriage and lower level of education, but no interaction between these. Presymptomatic mutation carriers of autosomal dominant AD showed no relation between APOE ε4 and Aβ burden, but increasing level of education was associated with reduced Aβ burden. The association between educational attainment and Aβ burden was similar in the 2 cohorts. CONCLUSIONS: While the APOE ε4 allele confers increased tendency toward Aβ accumulation in sporadic AD only, protective environmental factors, like increased education, may promote brain resistance against Aβ pathology in both sporadic and autosomal dominant AD. © 2020 American Academy of Neurology.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Pharmacological Treatments for Tinnitus-Reply” (2020) JAMA
Pharmacological Treatments for Tinnitus-Reply
(2020) JAMA, 324 (11), pp. 1109-1110.
Piccirillo, J.F.a b , Rodebaugh, T.L.c , Lenze, E.J.d
a Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine, St Louis, MO, United States
b Editor,
c Department of Psychology, Washington University, St Louis, MO, United States
d Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
Document Type: Article
Publication Stage: Final
Source: Scopus
“High-throughput single-cell functional elucidation of neurodevelopmental disease-associated genes reveals convergent mechanisms altering neuronal differentiation” (2020) Genome Research
High-throughput single-cell functional elucidation of neurodevelopmental disease-associated genes reveals convergent mechanisms altering neuronal differentiation
(2020) Genome Research, 30 (9), pp. 1317-1331.
Lalli, M.A.a b , Avey, D.a b , Dougherty, J.D.a c , Milbrandt, J.a , Mitra, R.D.a b
a Department of Genetics, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States
b Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States
c Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States
Abstract
The overwhelming success of exome- and genome-wide association studies in discovering thousands of disease-associated genes necessitates developing novel high-throughput functional genomics approaches to elucidate the molecular mechanisms of these genes. Here, we have coupled multiplexed repression of neurodevelopmental disease-associated genes to single-cell transcriptional profiling in differentiating human neurons to rapidly assay the functions of multiple genes in a disease-relevant context, assess potentially convergent mechanisms, and prioritize genes for specific functional assays. For a set of 13 autism spectrum disorder (ASD)-associated genes, we show that this approach generated important mechanistic insights, revealing two functionally convergent modules of ASD genes: one that delays neuron differentiation and one that accelerates it. Five genes that delay neuron differentiation (ADNP, ARID1B, ASH1L, CHD2, and DYRK1A) mechanistically converge, as they all dysregulate genes involved in cell-cycle control and progenitor cell proliferation. Live-cell imaging after individual ASD-gene repression validated this functional module, confirming that these genes reduce neural progenitor cell proliferation and neurite growth. Finally, these functionally convergent ASD gene modules predicted shared clinical phenotypes among individuals with mutations in these genes. Altogether, these results show the utility of a novel and simple approach for the rapid functional elucidation of neurodevelopmental disease-associated genes. © 2020 Lalli et al.; Published by Cold Spring Harbor Laboratory Press.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Sleep deprivation in an American homeless population” (2020) Sleep Health
Sleep deprivation in an American homeless population
(2020) Sleep Health, 6 (4), pp. 489-494.
Gonzalez, A.a , Tyminski, Q.b
a Washington University School of Medicine, Program in Occupational Therapy, St. Louis, MO, United States
b Washington University School of Medicine, Program in Occupational Therapy, St. Louis, MO, United States
Abstract
Background: The Centers for Disease Control and Prevention recently labeled sleep deprivation an epidemic in America with 35% of Americans reporting less than the recommended 7-9 hours of sleep each night. A recent study in France found that people experiencing homelessness sleep less and experience increased daytime fatigue as compared with the general population. Sleep intervention and research are rarely the focus for this population resulting in insufficient literature and knowledge to date on sleep health in people experiencing homelessness. Objectives: The objective of this study was to determine quality, quantity, supports, and barriers to sleep within a homeless population. Design: A mixed-methods survey was conducted to obtain data on sleep in the homeless population. Participants: 32 English-speaking adults experiencing homelessness were recruited from a local homeless organization. Measures: A web-based survey and two self-report standardized assessments were administered. Standardized assessments included Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0-Fatigue 13a and the PROMIS Short Form v1.0-Sleep Disturbance 8b. Results: Seventy-five percent of participants report getting less than the 7-9 recommended hours of sleep per night. Participants scored almost one standard deviation above the mean on both PROMIS measures demonstrating greater fatigue and sleep disturbance as compared with the general population. Four themes were identified via qualitative analysis: lack of environmental control, emotion and thought, substance use as a sleep aid, and sleep is important for health and daily function. Conclusions: Results indicate a need for sleep hygiene intervention within the homeless population. Sleep deprivation is a barrier to the population’s ability to obtaining housing. © 2020 National Sleep Foundation.
Author Keywords
Health; Homeless; Sleep; Sleep deprivation; Sleep insufficiency
Document Type: Article
Publication Stage: Final
Source: Scopus
“Heart rate variability biomarkers of leucine-rich repeat kinase 2-associated Parkinson’s disease” (2020) 2020 11th Conference of the European Study Group on Cardiovascular Oscillations: Computation and Modelling in Physiology: New Challenges and Opportunities, ESGCO 2020
Heart rate variability biomarkers of leucine-rich repeat kinase 2-associated Parkinson’s disease
(2020) 2020 11th Conference of the European Study Group on Cardiovascular Oscillations: Computation and Modelling in Physiology: New Challenges and Opportunities, ESGCO 2020, art. no. 9158194, .
Naranjo, C.C.b , Marras, C.c , Visanji, N.P.c , Cornforth, D.J.d , Sanchez-Rodriguez, L.e , Schule, B.f , Goldman, S.M.g , Estevez, M.h , Stein, P.K.i , Lang, A.E.c , Machado, A.j , Jelinek, H.F.a
a Khalifa University, Abu Dhabi, United Arab Emirates
b Vrije Universiteit Brussel (VUB), Brussels, 1050, Belgium
c Toronto Western Hospital, Toronto, ON M5T 2S8, Canada
d University of Newcastle, Callaghan, NSW 2308, Australia
e University of Calgary, Calgary, AB T2N 4N1, Canada
f Stanford School of Medicine, Stanford, CA 94305, United States
g University of California, San Francisco, CA 94118, United States
h Institute of Neurology and Neurosurgery, La Habana, 10400, Cuba
i Washington University, St. Louis, MO 63110, United States
j University of Havana, La Habana, 10400, Cuba
Abstract
Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common known cause of both familial and sporadic Parkinson’s disease (PD). On a single patient basis, LRRK2-associated PD (LRRK2-PD) and idiopathic PD (iPD) are indistinguishable. Recent evidence suggests that LRRK2-PD may be related to greater vagal activity. This study aimed to explore the potential of standard and novel heart rate variability (HRV) measures to distinguish LRRK2-PD from iPD patients. Support vector machine classifiers, based on HRV features, were used to discriminate between PD types. The combination of two classifiers reached 79% sensitivity and 86% specificity. Cardiac autonomic biomarkers may be useful to accurately distinguish individuals with LRRK2-PD from iPD. © 2020 IEEE.
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Pediatric ADHD symptom burden relates to distinct neural activity across executive function domains” (2020) NeuroImage: Clinical
Pediatric ADHD symptom burden relates to distinct neural activity across executive function domains
(2020) NeuroImage: Clinical, 28, art. no. 102394, .
Nugiel, T.a , Roe, M.A.a , Engelhardt, L.E.a , Mitchell, M.E.b , Zheng, A.c , Church, J.A.a d
a Department of Psychology, The University of Texas at Austin, Austin, TX, United States
b Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Biomedical Imaging Center, The University of Texas at Austin, Austin, TX, United States
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent childhood disorder marked by inattention and/or hyperactivity symptoms. ADHD may also relate to impaired executive function (EF), but is often studied in a single EF task per sample. The current study addresses the question of unique vs. overlapping relations in brain activity across multiple EF tasks and ADHD symptom burden. Three in-scanner tasks drawn from distinct EF domains (cognitive flexibility, working memory, and inhibition) were collected from children with and without an ADHD diagnosis (N = 63). Whole-brain activity and 11 regions of interest were correlated with parent reports of inattention and hyperactivity symptoms. Across the three EF domains, brain activity related to ADHD symptom burden, but the direction and location of these associations differed across tasks. Overall, activity in sensory and default mode network regions related to ADHD, and these relations did not consistently overlap across EF domains. We observed both distinct and overlapping patterns for inattention and hyperactivity symptoms. By studying multiple EF tasks in the same sample, we identified a heterogenous neural profile related to attention symptom burden in children. Our results inform ADHD characterization and treatment and explain some of the variable brain results related to EF and ADHD reported in the literature. © 2020 The Authors
Author Keywords
ADHD; Development; Executive functions; fMRI; Hyperactivity; Inattention
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Putative COVID- 19 Induction of Reward Deficiency Syndrome (RDS) and Associated Behavioral Addictions with Potential Concomitant Dopamine Depletion: Is COVID-19 Social Distancing a Double Edged Sword?” (2020) Substance Use and Misuse
Putative COVID- 19 Induction of Reward Deficiency Syndrome (RDS) and Associated Behavioral Addictions with Potential Concomitant Dopamine Depletion: Is COVID-19 Social Distancing a Double Edged Sword?
(2020) Substance Use and Misuse, .
Blum, K.a b c d , Cadet, J.L.e , Baron, D.a , Badgaiyan, R.D.f , Brewer, R.c , Modestino, E.J.g , Gold, M.S.h
a Graduate College, Western University Health Sciences, Pomona, CA, United States
b Department Psychiatry, Boonshoff School of Medicine, Wright University, Dayton, OH, United States
c Division of Nutrigenomics, Geneus Genomic Testing Center, Geneus Health, LLC, San Antonio, TX, United States
d Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
e Molecular Neuropsychiatry Research Branch, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, United States
f Department of Psychiatry, Long School of Medicine, University of Texas Health Science Center, San Antonio, TX, United States
g Department of Psychology, Curry College, Milton, MA, United States
h Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO, United States
Abstract
Background: The overwhelming fatalities of the global COVID-19 Pandemic will have daunting epigenetic sequala that can translate into an array of mental health issues, including panic, phobia, health anxiety, sleep disturbances to dissociative like symptoms including suicide. Method: We searched PUBMED for articles listed using the search terms “COVID 19 Pandemic”, COVID19 and genes,” “stress and COVID 19”, Stress and Social distancing: Results: Long-term social distancing may be neurologically harmful, the consequence of epigenetic insults to the gene encoding the primary receptor for SARS-CoV2, and COVID 19. The gene is Angiotensin I Converting-Enzyme 2 (ACE2). According to the multi-experiment matrix (MEM), the gene exhibiting the most statistically significant co-expression link to ACE2 is Dopa Decarboxylase (DDC). DDC is a crucial enzyme that participates in the synthesis of both dopamine and serotonin. SARS-CoV2-induced downregulation of ACE2 expression might reduce dopamine and serotonin synthesis, causing hypodopaminergia. Discussion: Indeed, added to the known reduced dopamine function during periods of stress, including social distancing the consequence being both genetic and epigenetic vulnerability to all Reward Deficiency Syndrome (RDS) addictive behaviors. Stress seen in PTSD can generate downstream alterations in immune functions by reducing methylation levels of immune-related genes. Conclusion: Mitigation of these effects by identifying subjects at risk and promoting dopaminergic homeostasis to help regulate stress-relative hypodopaminergia, attenuate fears, and prevent subsequent unwanted drug and non-drug RDS type addictive behaviors seems prudent. © 2020 Taylor & Francis Group, LLC.
Author Keywords
behavioral addiction; COVID-19 pandemic; dopamine homeostasis; epigenetic insults; immunologic function; mental illness; stress
Document Type: Note
Publication Stage: Article in Press
Source: Scopus
“Cognitive science of religion and the study of islam: Rethinking islamic theology, law, education, and mysticism using the works of al-ghazālī” (2020) Method and Theory in the Study of Religion
Cognitive science of religion and the study of islam: Rethinking islamic theology, law, education, and mysticism using the works of al-ghazālī
(2020) Method and Theory in the Study of Religion, 32 (3), pp. 205-232.
Nakissa, A.
Department of Jewish, Islamic, and Middle Eastern Studies, Washington University, St. Louis, MO, United States
Abstract
Specialists in Islamic studies have taken virtually no interest in the influential and rapidly developing field of Cognitive Science of Religion (CSR). The present article seeks to address this problem by considering how insights from CSR can be systematically applied to reconceptualize Islamic theology, law, education, and mysticism. The article centers on what is probably CSR’s most influential and well-established idea; namely, that religion is closely linked to an evolved “mindreading” ability (i.e., a “Theory of Mind Module”). It is argued that Islamic theology employs mindreading focused on events and objects in the universe, Islamic law and education employ mindreading focused on scriptural texts and embodied practices, and Islamic mysticism employs mindreading focused on psychological experiences. The article develops these ideas through an analysis of the Arabic-language writings of Abū Hāmid al-Ghazālī, the famous medieval Islamic theologian, jurist, and mystic. © 2020 Brill Academic Publishers. All rights reserved.
Author Keywords
Cognitive science; Education; Islam; Law; Mysticism; Theology
Document Type: Review
Publication Stage: Final
Source: Scopus
“Recommendations and Alerting for Delirium Alleviation in Real-Time (RADAR): Protocol for a pilot randomized controlled trial” (2020) F1000Research
Recommendations and Alerting for Delirium Alleviation in Real-Time (RADAR): Protocol for a pilot randomized controlled trial
(2020) F1000Research, 8, art. no. 1683, .
Vlisides, P.E.a b , Ragheb, J.W.a , Leis, A.a , Schoettinger, A.c , Hickey, K.d , McKinney, A.a , Brooks, J.a , Zierau, M.a , Norcott, A.e f , Yang, S.a , Avidan, M.S.g , Min, L.e h
a Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48170, United States
b Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109, United States
c Department of Social Work, Michigan Medicine, Ann Arbor, MI 48109, United States
d University of Michigan School of Nursing, Ann Arbor, MI 48109, United States
e Department of Internal Medicine, Division of Geriatric and Palliative Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, United States
f Department of Internal Medicine, Division of Geriatric and Palliative Medicine, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48105, United States
g Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
h Geriatric Research Education and Clinical Care, VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, United States
Abstract
Background: Delirium is a common and serious complication of major surgery for older adults. Postoperative social and behavioral support (e.g., early mobilization, mealtime assistance) may reduce the incidence and impact of delirium, and these efforts are possible with proactive patient-care programs. This pilot trial tests the hypothesis that a multicomponent decision support system, which sends automated alerts and recommendations to patient-care programs and family members for high-risk patients, will improve the postoperative environment for neurocognitive and clinical recovery. Methods: This will be a randomized, controlled, factorial pilot trial at a large academic medical center. High-risk, non-cardiac surgery patients (≥70 years old) will be recruited. Patients will be allocated to a usual care group (n=15), Hospital Elder Life Program (HELP)-based paging system (n=15), family-based paging system (n=15), or combined HELP- and family-based system (n=15). The primary outcome will be the presence of delirium, defined by positive long-form Confusion Assessment Method screening. Secondary outcomes will include additional HELP- and family-based performance metrics along with various neurocognitive and clinical recovery measures. Exploratory outcomes include the incidence of positive family-based delirium assessments post-discharge, 36-item Short Form Survey, PROMIS Cognitive Function Abilities Subset 4a, and 30-day readmission rates. Ethics and dissemination: This trial has received approval by the University of Michigan Medical Institutional Review Board (IRBMED). Dissemination plans include presentation at scientific conferences, publication in medical journals, and distribution via educational and news media. Registration: ClinicalTrials.gov Identifier NCT04007523, registered on 7/3/2019. © 2020 Vlisides PE et al.
Author Keywords
Clinical Trial Protocol; Decision Support Systems; Delirium; Feasibility Studies; Perioperative Care
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Rapidly-Customizable, Scalable 3D-Printed Wireless Optogenetic Probes for Versatile Applications in Neuroscience” (2020) Advanced Functional Materials
Rapidly-Customizable, Scalable 3D-Printed Wireless Optogenetic Probes for Versatile Applications in Neuroscience
(2020) Advanced Functional Materials, .
Lee, J.a , Parker, K.E.b c d , Kawakami, C.e , Kim, J.R.b c d , Qazi, R.a , Yea, J.f , Zhang, S.g , Kim, C.Y.a , Bilbily, J.b c d , Xiao, J.g , Jang, K.-I.f , McCall, J.G.b c d , Jeong, J.-W.a
a School of Electrical Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea
b Department of Anesthesiology, Washington University Pain Center, Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, United States
c Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO 63130, United States
d Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University School of Medicine, St. Louis, MO 63130, United States
e Department of Electrical and Electronic Information Engineering, Toyohashi University of Technology, Toyohashi, 441-8580, Japan
f Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, South Korea
g Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO 80309, United States
Abstract
Optogenetics is an advanced neuroscience technique that enables the dissection of neural circuitry with high spatiotemporal precision. Recent advances in materials and microfabrication techniques have enabled minimally invasive and biocompatible optical neural probes, thereby facilitating in vivo optogenetic research. However, conventional fabrication techniques rely on cleanroom facilities, which are not easily accessible and are expensive to use, making the overall manufacturing process inconvenient and costly. Moreover, the inherent time-consuming nature of current fabrication procedures impede the rapid customization of neural probes in between in vivo studies. Here, a new technique stemming from 3D printing technology for the low-cost, mass production of rapidly customizable optogenetic neural probes is introduced. The 3D printing production process, on-the-fly design versatility, and biocompatibility of 3D printed optogenetic probes as well as their functional capabilities for wireless in vivo optogenetics is detailed. Successful in vivo studies with 3D printed devices highlight the reliability of this easily accessible and flexible manufacturing approach that, with advances in printing technology, can foreshadow its widespread applications in low-cost bioelectronics in the future. © 2020 Wiley-VCH GmbH
Author Keywords
3D printing; microfabrication; neural probes; optogenetics; wireless probes
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Concepts and predication from perception to cognition” (2020) Nous-Supplement: Philosophical Issues
Concepts and predication from perception to cognition
(2020) Nous-Supplement: Philosophical Issues, .
Quilty-Dunn, J.a b
a University of Oxford, United Kingdom
b Washington University in St. Louis, United States
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Novel low-shot deep learning approach for retinal image classification with few examples” (2020) JAMA Ophthalmology
Novel low-shot deep learning approach for retinal image classification with few examples
(2020) JAMA Ophthalmology, pp. E1-E2.
Hunt, M.S.a b , Kihara, Y.a , Lee, A.Y.a
a Department of Ophthalmology, School of Medicine, University of Washington, Seattle, United States
b School of Medicine, Washington University, St Louis, MO, United States
Document Type: Note
Publication Stage: Article in Press
Source: Scopus
“Typologies of illicit drug use in mid-adulthood: a quasi-longitudinal latent class analysis in a community-based sample of twins” (2020) Addiction
Typologies of illicit drug use in mid-adulthood: a quasi-longitudinal latent class analysis in a community-based sample of twins
(2020) Addiction, .
Dash, G.F.a , Martin, N.G.b , Agrawal, A.c , Lynskey, M.T.d , Slutske, W.S.a
a Department of Psychological Sciences, University of Missouri, Columbia, MO, United States
b QIMR Berghofer, Brisbane, QLD, Australia
c Washington University School of Medicine, St. Louis, MO, United States
d King’s College London Institute of Psychiatry, London, United Kingdom
Abstract
Aims: To identify drug use typologies based on substances used and persistence of use over two time points, use a genetically informed design to explore twin concordance of and genetic influence on the use typologies and compare patterns of declined/discontinued (“desistant”) and persistent drug use on drug use correlates. Design: Latent class analysis was applied to data from a cross-sectional self-report survey on current and past drug use. Use characteristics, use disorder, and psychiatric problems were compared across classes. Setting: Computer-assisted telephone interview in respondents’ homes. Participants: A total of 3785 individual twins and siblings (1365 men, 2420 women; Mage = 32) from the Australian Twin Registry Cohort III. Measurements: A comprehensive interview assessed prior to past year and past year use of cannabis, stimulants, cocaine/crack, hallucinogens, opioids, sedatives, inhalants, dissociatives, and solvents; age of first use; opportunity to use; peer drug use; attention deficit/hyperactivity, conduct, antisocial personality, depressive, and substance use disorders; and suicidality. Findings: A five-class solution emerged: no/low use (50%), desistant cannabis use (23%), desistant party drug use (18%), persistent prescription drug misuse (4%), and persistent polydrug use (5%). Twin concordances were higher among monozygotic (k = 0.30–0.35) than dizygotic pairs (same-sex k = 0.19–0.20; opposite sex k = 0.07), and biometric modeling suggested that the persistent polydrug use class, in particular, was highly heritable (a2 = 0.94). Conduct disorder (OR = 2.40), antisocial personality disorder (OR = 3.27), and suicidal ideation (OR = 1.98) increased persistent polydrug use risk; depression (OR = 2.38) and lifetime suicide attempt (OR = 2.31) increased persistent prescription misuse risk. Relative to persistent prescription drug misuse, persistent polydrug use was associated with higher rates of cannabis and stimulant use disorder (OR = 6.14–28.01), younger first substance use (OR = 0.82–0.83), more drug use opportunity (OR = 10.66–66.06), and more drug-using peers (OR = 4.66–9.20). Conclusions: Unique patterns of declined/discontinued (“desistant”) and persistent drug use are differentially heritable and differentially associated with risk factors, psychiatric symptoms, and substance use disorder outcomes. © 2020 Society for the Study of Addiction
Author Keywords
Illicit drugs; latent class analysis; persistent drug use; polydrug use; quasi-longitudinal; twin study
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Functional Connectivity Decreases with Metabolic Stress in Sickle Cell Disease” (2020) Annals of Neurology
Functional Connectivity Decreases with Metabolic Stress in Sickle Cell Disease
(2020) Annals of Neurology, .
Fields, M.E.a , Mirro, A.E.a , Guilliams, K.P.a b , Binkley, M.M.b , Gil Diaz, L.b , Tan, J.a , Fellah, S.b , Eldeniz, C.c , Chen, Y.b , Ford, A.L.b c , Shimony, J.S.c , King, A.A.a d , An, H.c , Smyser, C.D.a b c , Lee, J.-M.b c e
a Department of Pediatrics, 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 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d Program of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
e Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Objective: Children with sickle cell disease (SCD) experience cognitive deficits even when unaffected by stroke. Using functional connectivity magnetic resonance imaging (MRI) as a potential biomarker of cognitive function, we tested our hypothesis that children with SCD would have decreased functional connectivity, and that children experiencing the greatest metabolic stress, indicated by elevated oxygen extraction fraction, would have the lowest connectivity. Methods: We prospectively obtained brain MRIs and cognitive testing in healthy controls and children with SCD. Results: We analyzed data from 60 participants (20 controls and 40 with sickle cell disease). There was no difference in global cognition or cognitive subdomains between cohorts. However, we found decreased functional connectivity within the sensory-motor, lateral sensory-motor, auditory, salience, and subcortical networks in participants with SCD compared with controls. Further, as white matter oxygen extraction fraction increased, connectivity within the visual (p = 0.008, parameter estimate = −0.760 [95% CI = −1.297, −0.224]), default mode (p = 0.012, parameter estimate = −0.417 [95% CI = −0.731, −0.104]), and cingulo-opercular (p = 0.009, parameter estimate = −0.883 [95% CI = −1.517, −0.250]) networks decreased. Interpretation: We conclude that there is diminished functional connectivity within these anatomically contiguous networks in children with SCD compared with controls, even when differences are not seen with cognitive testing. Increased white matter oxygen extraction fraction was associated with decreased connectivity in select networks. These data suggest that elevated oxygen extraction fraction and disrupted functional connectivity are potentially presymptomatic neuroimaging biomarkers for cognitive decline in SCD. ANN NEUROL 2020. © 2020 American Neurological Association
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons” (2020) Nature Immunology
Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons
(2020) Nature Immunology, . Cited 2 times.
Alves de Lima, K.a b c , Rustenhoven, J.a b c , Da Mesquita, S.a b , Wall, M.a b , Salvador, A.F.a b c , Smirnov, I.a b c , Martelossi Cebinelli, G.a b d , Mamuladze, T.a b c , Baker, W.a b , Papadopoulos, Z.a b c , Lopes, M.B.e , Cao, W.S.f , Xie, X.S.f , Herz, J.a b c , Kipnis, J.a b c
a Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA, United States
b Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA, United States
c Department of Pathology and Immunology, Division of Immunobiology, Washington University, St. Louis, MO, United States
d Center for Research on Inflammatory Diseases (CRID), Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
e Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, United States
f AfaSci Research Laboratories, Redwood City, CA, United States
Abstract
Interleukin (IL)-17a has been highly conserved during evolution of the vertebrate immune system and widely studied in contexts of infection and autoimmunity. Studies suggest that IL-17a promotes behavioral changes in experimental models of autism and aggregation behavior in worms. Here, through a cellular and molecular characterization of meningeal γδ17 T cells, we defined the nearest central nervous system–associated source of IL-17a under homeostasis. Meningeal γδ T cells express high levels of the chemokine receptor CXCR6 and seed meninges shortly after birth. Physiological release of IL-17a by these cells was correlated with anxiety-like behavior in mice and was partially dependent on T cell receptor engagement and commensal-derived signals. IL-17a receptor was expressed in cortical glutamatergic neurons under steady state and its genetic deletion decreased anxiety-like behavior in mice. Our findings suggest that IL-17a production by meningeal γδ17 T cells represents an evolutionary bridge between this conserved anti-pathogen molecule and survival behavioral traits in vertebrates. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus