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Neural Regeneration Research 2019年第5期14卷 757-761页

作者： Abraam M.Yakoub Department of Molecular and Cellular Physiology Stanford University

Multiple protocols have been devised to generate cerebral organoids that recapitulate features of the developing human brain, including the presence of a large, multi-layered, cortical-like neuronal zone. However, the central question is whether these organoids truly present mature, functional neurons and astrocytes, which may qualify the system for in-depth molecular neuroscience studies focused at neuronal and synaptic functions. Here, we demonstrate that cerebral organoids derived under optimal differentiation conditions exhibit mature, fully functional neurons and astrocytes, as validated by immunohistological, gene expression, and electrophysiological, analyses. Neurons in cerebral organoids showed gene expression profiles and electrophysiological properties similar to those reported for fetal human brain. These important findings indicate that cerebral organoids recapitulate the developing human brain and may enhance use of cerebral organoids in modeling human brain development or investigating neural deficits that underlie neurodevelopmental and neuropsychiatric conditions, such as autism or intellectual disorders.

关键词： cerebral organoids human brain stem cells neurons astrocytes neurodevelopmental disorders neuropsychiatric disorders autism

RhoGEF Trio Regulates Radial Migration of Projection Neurons via Its Distinct Domains

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Neuroscience Bulletin 2022年第3期38卷 249-262页

作者： Chengwen Wei Mengwen Sun Xiaoxuan Sun Hu Meng Qiongwei Li Kai Gao Weihua Yue Lifang Wang Dai Zhang Jun Li Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Beijing100191China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing100871China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing100871China Chinese Institute for Brain Research Beijing100010China Institute for Brain Research and Rehabilitation(IBRR) Guangdong Key Laboratory of Mental Health and Cognitive ScienceSouth China Normal UniversityGuangzhou510631China

The radial migration of cortical pyramidal neurons(PNs)during corticogenesis is necessary for establishing a multilayered cerebral *** migration defects are considered a critical etiology of neurodevelopmental disorders,including autism spectrum disorders(ASDs),schizophrenia,epilepsy,and intellectual disability(ID).TRIO is a high-risk candidate gene for ASDs and ***,its role in embryonic radial migration and the etiology of ASDs and ID are not fully *** this study,we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born *** investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin(N-cadherin).Also,independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent *** together,our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 *** results suggest the vital roles of the guanine nucleotide exchange factor 1(GEF1)and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners,which might be associated with the abnormal phenotypes in neurodevelopmental disorders.

关键词： Trio Myosin X RhoGEF neurodevelopmental disorder Radial migration

Omega-3 fatty acids and mental health

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Global Health Journal 2020年第1期4卷 18-30页

作者： Klaus W.Lange Institute of Psychology University of Regensburg93040 RegensburgGermany

Nutrition plays a key role in brain development,mental health,and psychiatric *** role of omega-3 polyunsaturated fatty acids in physical health is well established,and their role in mental health is becoming increasingly ***-3 fatty acids are involved in a wide range of physiological functions that are related to neurogenesis,neurotransmission,and neuroinflammation;therefore,they play fundamental roles in the development,functioning,and aging of the *** humans,dietary deficiencies of omega-3 fatty acids are associated with an increased risk of developing various psychiatric disorders,including depression,bipolar disorder,schizophrenia,dementia,attention-deficit/hyperactivity disorder,and *** particular,eicosapentaenoic and docosahexaenoic acid have been linked to the maintenance of mental health,and their deficits have been implicated in the pathophysiology of mental *** may be mediated by the modulation of inflammatory processes and their direct effects on neuronal membrane fluidity and receptor ***,randomized clinical trials that have investigated the therapeutic effects of omega-3 fatty acids have yielded inconclusive results,thereby limiting the use of these nutrients in psychiatric ***-quality clinical trials should be conducted to examine the efficacy of omega-3 fatty acids in preventing and treating mental *** undesirable side effects of omega-3 fatty acid supplementation should also be *** effects may become apparent after many years of administration,and therefore,they may not be detected in most cases.

关键词： Omega-3 fatty acids Mental health neurodevelopmental disorders Dementia Depression Schizophrenia

Mapping Contaminants Associated with Autism: A Public Health Pilot in New Jersey

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Journal of Geographic Information System 2014年第6期6卷 706-722页

作者： Erin Speiser Ihde Themba Nyirenda Aridaman K. Jain Ji Meng Loh Francisco Artigas Christine Hobble Dom Elefante Saleh Kojak Jin Young Shin Lawrence Rosen The Deirdre Imus Environmental Health Center Hackensack University Medical Center Hackensack USA Department of Research David & Alice Jurist Institute for Research Hackensack University Medical Center Hackensack USA Department of Mathematical Sciences NJ Institute of Technology Newark USA Meadowlands Environmental Research Institute New Jersey Meadowlands Commission Lyndhurst USA

The rise in reported prevalence rates of autism spectrum disorders (ASDs) is a national concern that continues to grow at a record pace. New Jersey has the highest prevalence rate of autism spectrum disorders (ASDs) among states surveyed, with approximately 1 in 45 children diagnosed. The pilot study focused on toxins potentially linked to autism: arsenic, lead, manganese, mercury, organophosphate pesticides, polychlorinated biphenyls, trichloroethylene, and vinyl chloride. In northern NJ there were approximately 4600 Known Contaminated Sites (KCSNJ) where these toxins were detected. A total of 269,790 sample detections were identified. Our objective was to identify and map these sites, and identify methods by which more robust contaminant data could be collected and analyzed. This study resulted in eight original maps showing sample detections. These maps will aid researchers and public health advocates in future analyses exploring links between autism and these toxins. Concentrations of multiple toxins associated with ASDs were most dense near urban industrial or mixed residential/industrial areas, though no conclusions can be made regarding association or causality between the sample detections and autism. Based in part on this study, NJDEP has made and will continue to make improvements to contaminant data collection systems.

关键词： ASD Autism Contaminant neurodevelopmental Toxin

Autism and carnitine: A possible link

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World Journal of Biological Chemistry 2019年第1期10卷 7-16页

作者： Caroline Demarquoy Jean Demarquoy DATSA 71 - Foyer Marie-José Marchand Université de Bourgogne-Agrosup Dijon UMR PAM

Patients with autism spectrum disorders(ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD have not been defined yet. Many factors seem to be involved in the onset of this disorder. These include genetic and environmental factors, but autism is not linked to a single origin, only. Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency. Carnitine is a derivative of two amino acid lysine and methionine. Carnitine is a cofactor for a large family of enzymes: the carnitine acyltransferases. Through their action these enzymes(and L-carnitine) are involved in energy production and metabolic homeostasis. Some people with autism(less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with Lcarnitine is beneficial. This review summarizes the available information on this topic.

关键词： Autism Carnitine neurodevelopmental Metabolism Pathophysiological bases

Calcium and Magnesium Levels Are down Regulated in Nigerian Children with Autism Spectrum Disorder and Cerebral Palsy

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Neuroscience & Medicine 2018年第3期9卷 159-170页

作者： Ishiaq Olayinka Omotosho Adekunbi Olufunke Akinade Ikeoluwa Abiola Lagunju Department of Chemical Pathology College of Medicine University of Ibadan Ibadan Nigeria Department of Paediatrics College of Medicine University of Ibadan Ibadan Nigeria

Autism Spectrum Disorders (ASDs) and Cerebral Palsy (CP) are amongst the leading neurodevelopmental disorders in children worldwide causing diminished quality of life. Unlike CP caused by brain damage affecting muscle tone, movement and motor skills, equivocal report of different genes with varying loci as genetic malformation and genetic modulation by environmental factors have been the focus of attention in the aetiology of ASD. This study investigated levels of toxic metal (Pb) and macro elements (Ca and Mg) in blood of children with ASD and CP in Nigeria. 8 and 18 Children (aged 2 - 12 years) clinically screened for features of ASD and CP respectively by pediatric neurologist using DMS-IV classification along with 15 age-matched neurologically healthy ones as controls were recruited. Plasma levels of Ca, Mg and Pb were determined in the children using Induction Coupled Plasma Mass Spectroscopy (ICP-MS). Results were analyzed using students t-test. The gender difference was not significant in the children (P = 0.216) while developmental milestones’ abnormalities (stable neck, sitting, crawling and walking) was significantly prevalent among CP children relative to ASD and normal children (P= 0.003, 0.003, 0.003 and 0.000 respectively);however, abnormality in talking was common in ASD and CP relative to normal children (P = 0.000). There was significant difference in educational background of ASD and CP parents relative to those of normal children (P = 0.025). Mean plasma calcium and magnesium levels was significantly reduced in children with ASD (7.90 ± 0.17 mg/dl, 2.44 ± 0.07 mg/dl) and CP (7.26 ± 0.31 mg/dl, 2.42 ± 0.08 mg/dl) in comparison to the controls (8.97 ± 0.20 mg/dl and 3.26 ± 0.16 mg/dl);(P < 0.001;P < 0.000 and P < 0.002;P < 0.000) respectively. However, mean lead levels in children with CP (10.38 ± 1.45 μg/dl) were significantly greater than in ASD (7.92 ± 1.30 μg/dl) and normal children (6.83 ± 0.72 μg/dl) (P < 0.433;P < 0.047). Hypocalcaemia and hy

关键词： ASD CP Calcium Magnesium Lead neurodevelopmental Disorders

Temporal Memory Dysfunction and Alterations in Tyrosine Hydroxylase Immunoreactivity in Adult Rats Following Neonatal Exposure to Domoic Acid

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Neuroscience & Medicine 2013年第1期4卷 29-35页

作者： Mark A. Robbins Catherine L. Ryan Amber L. Marriott Tracy Ann Doucette Departments of Biology University of Prince Edward Charlottetown Canada Departments of Psychology University of Prince Edward Charlottetown Canada

The purpose of the present study was to determine whether early alterations in glutamate signaling, via daily injections of the glutamate agonist, domoic acid (DOM;20 μg/kg), during a critical period of CNS development (PND 8 - 14), would result in temporal memory deficits and/or alterations in tyrosine hydroxylase (TH) immunoreactivity. As adults, subjects were assessed for temporal memory ability using a recency discrimination paradigm. Both number and duration of exploratory contacts directed at familiar objects, differing by one hour in recall delay, were measured. Analyses revealed that DOM-treated females demonstrated temporal memory dysfunction, as evidenced in a significantly lower proportion of total exploratory behaviour directed toward the remote object. Integrity of the dopamine system was assessed using immunohistochemistry to examine TH immunoreactivity in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Sections obtained from DOM-treated males had significantly less TH immunoreactivity in the right mPFC, while DOM-treated females had significantly greater TH immunoreactivity in the left core and right shell of the NAcc. These findings are discussed in context of early alterations to glutamate signaling in the development of human neuropsychiatric disorders.

关键词： Domoic Acid Glutamate Schizophrenia Animal Models neurodevelopmental Disorders

Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study

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World Journal of Psychiatry 2016年第4期6卷 419-430页

作者： Vladeta Ajdacic-Gross Aleksandra Aleksandrowicz Stephanie Rodgers Margot Mutsch Anja Tesic Mario Müller Wolfram Kawohl Wulf R?ssler Erich Seifritz Enrique Castelao Marie-Pierre F Strippoli Caroline Vandeleur Roland von K?nel Rosa Paolicelli Markus A Landolt Cornelia Witthauer Roselind Lieb Martin Preisig Department of Psychiatry Psychotherapy and Psychosomatics Psychiatric Hospital University of Zurich Epidemiology Biostatistics and Prevention Institute University of Zurich Department of Psychiatry University Hospital of Lausanne Department of Neurology Bern University Hospital Clinic Barmelweid Division of Psychiatry Research University of Zurich University Children’s Hospital Zurich and Children’s Research Center and Division of Child and Adolescent Health Psychology Department of Psychology University of Zurich Department of Psychology Division of Clinical Psychology and Epidemiology University of Basel

AIM To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk *** We used data from PsyC oL aus, a large Swiss Population Cohort Study(n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: neurodevelopmental, anxiety(early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects. RESULTS Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders(men), and measles/mumps/rubella-infections with early and late anxiety disorders(women). Gastric inflammatory diseases took effect in mood disorders(both sexes) and in early disorders(men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne(associations with mood disorders in men) and psoriasis(associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders(men), and neurodevelopmental and early anxiety disorders(women).CONCLUSION Infectious, atopic and inflammatory diseases areimportant risk factors for all groups of mental disorde

关键词： neurodevelopmental disorders Mental disorders Substance abuse Childhood diseases Infectious diseases Atopic diseases Chronic inflammatory diseases Risk factors