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Contactins in the central nervous system: role in health and disease

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Neural Regeneration Research 2019年第2期14卷 206-216页

作者： Madhurima Chatterjee Detlev Schild Charlotte E.Teunissen Amsterdam UMC VU University Medical Center Department of Clinical Chemistry Amsterdam Neuroscience Institute of Neurophysiology and Cellular Biophysics University of G?ttingen DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) University of G?ttingen DFG Excellence Cluster 171 University of G?ttingen

Contactins are a group of cell adhesion molecules that are mainly expressed in the brain and play pivotal roles in the organization of axonal domains, axonal guidance, neuritogenesis, neuronal development, synapse formation and plasticity, axo-glia interactions and neural regeneration. Contactins comprise a family of six members. Their absence leads to malformed axons and impaired nerve conduction. Contactin mediated protein complex formation is critical for the organization of the axon in early central nervous system development. Mutations and differential expression of contactins have been identified in neuro-developmental or neurological disorders. Taken together, contactins are extensively studied in the context of nervous system development. This review summarizes the physiological roles of all six members of the Contactin family in neurodevelopment as well as their involvement in neurological/neurodevelopmental disorders.

关键词： cell adhesion molecule Contactins axonal domain,neurogenesis synaptogenesis autism spectrum disorder neuro-developmental disorder neurological disease

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Dysregulation of neurogenesis by neuroinflammation:key differences in neurodevelopmental and neurological disorders

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Neural Regeneration Research 2017年第3期12卷 366-371页

作者： Lir-Wan Fan Yi Pang ackson MSUSA

Embryonic neurogenesis is the process of generating neurons,the functional units of the brain.Because of its sensitivity to adverse intrauterine environment such as infection,dysregulation of this process has emerged as a key mechanism underlying many neurodevelopmental disorders such as autism spectrum disorders（ASD）.Adult neurogenesis,although is restricted to a few neurogenic niches,plays pivotal roles in brain plasticity and repair.Increasing evidence suggests that impairments in adult neurogenesis are involved in major neurodegenerative disorders such as Alzheimer＇s disease.A hallmark feature of these brain disorders is neuroinflammation,which can either promote or inhibit neurogenesis depending upon the context of brain microenvironment.In this review paper,we present evidence from both experimental and human studies to show a complex picture of relationship between these two events,and discussed potential factors contributing to different or even opposing actions of neuroinflammation on neurogenesis in neurodevelopmental and neurological disorders.

关键词： microglia neurodegeneration autism embryonic neurogenesis adult neurogenesis cytokine aging

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Cerebral organoids exhibit mature neurons and astrocytes and recapitulate electrophysiological activity of the human brain

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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

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Prescription trends in children with pervasive developmental disorders:a claims data-based study in Japan

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世界儿科杂志:英文版 2016年第4期12卷 443-449页

作者： Michihiro Satoh Taku Obara Hidekazu Nishigori Nobuhiro Ooba Yoshihiko Morikawa Mami Ishikuro Hirohito Metoki Masahiro Kikuya Nariyasu Mano Department of Pharmaceutical Sciences Tohoku University HospitalSendaiJapan Department of Preventive Medicine and Epidemiology Tohoku Medical Megabank OrganizationTohoku University2-1 Seiryo-choAoba-kuSendaiMiyagi 980-8575Japan Division of Molecular Epidemiology Tohoku University Graduate School of MedicineSendaiJapan Department of Obstetrics and Gynecology Tohoku University Graduate School of MedicineSendaiJapan School of Pharmacy Nihon UniversityChibaJapan Clinical Research Support Center Tokyo Metropolitan Children’s Medical CenterTokyoJapan Department of Community Medical Supports Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan

Background:The only drug approved for pervasive developmental disorders(PDD)in Japan is pimozide.Several psychotropic drugs are also prescribed for offlabel use in Japan,but details regarding their prescription and use are largely unknown.The purpose of this study was to clarify the use of drug treatment in Japanese children with PDD.Methods:Data were extracted from claims data from the Japan Medical Data Center for children younger than 18 years of age who were newly diagnosed with PDD(International Classification of Diseases version 10 codes:F84)from 2005 to 2010(total of 3276 patients as of 2010).The prescription rates were presented as the percentage of PDD patients who were prescribed each drug.Results:Prior to 2010,the prescription rates for atypical antipsychotics,other antipsychotics,psychostimulants,all other central nervous system drugs,anticovnvulsants,non-barbiturates,and Parkinson’s disease/syndrome drugs significantly increased among the Anatomical Therapeutic Chemical classifications defined as the“nervous system”(trend P≤0.02).The prescription rate for risperidone consistently increased,reaching 6.9%in 2010(trend P<0.0001),the highest rate of the surveyed drugs among the antipsychotics.The prescription rate for aripiprazole also increased(trend P<0.0001),reaching 1.9%in 2010.The prescription rate for pimozide showed no annual changes,with a low rate of 0.4%in 2010.Conclusion:Compared with pimozide,the prescription rates for risperidone,aripiprazole and other psychotropic drugs have increased.Because safety data for these drugs in Japanese children are sparse,there is a need for future safety evaluations of these drugs in Japanese children.

关键词： autism children pervasive developmental disorders prescription

Pathophysiology of autism spectrum disorders:Revisiting gastrointestinal involvement and immune imbalance

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World Journal of Gastroenterology 2014年第29期20卷 9942-9951页

作者： Mohtashem Samsam Raheleh Ahangari Saleh A Naser Burnett School of Biomedical Sciences (BSBS) College of MedicineUniversity of Central Florida

autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.

关键词： autism spectrum disorders Gastrointestinal abnorma

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“autism”的本土化译名探讨

心理月刊 2023年第12期 186-188页

作者：高琳吴心怡韩许高南京中医药大学医学院整合医学学院南京中医药大学第一临床医学院南京中医药大学医学人文学院

本文对于近年来“autism”的“一词两译”现象，即“自闭症”与“孤独症”的混用问题进行了讨论。本文将从“官方性”“权威性”和“科学性”这3个维度提出意见，否定“孤独症”是“autism”的正确译名，证明“自闭症”不仅是正确的译... 详细信息

本文对于近年来“autism”的“一词两译”现象，即“自闭症”与“孤独症”的混用问题进行了讨论。本文将从“官方性”“权威性”和“科学性”这3个维度提出意见，否定“孤独症”是“autism”的正确译名，证明“自闭症”不仅是正确的译名，而且是没有歧视性含义的。

关键词： autism 一词两译孤独症自闭症

Potential for treatment of severe autism in tuberous sclerosis complex

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World Journal of Clinical Pediatrics 2013年第3期2卷 16-25页

作者： Tanjala T Gipson Gwendolyn Gerner Mary Ann Wilson Mary E Blue Michael V Johnston Tuberous Sclerosis Clinic Kennedy Krieger Institute Department of Neurology and Developmental Medicine Kennedy Krieger Institute Clinical Trials Unit Kennedy Krieger Institute Neuroscience Laboratory Hugo W. Moser Research InstituteInc.Kennedy Krieger Institute Department of Neurology Johns Hopkins University School of Medicine Department of Neuroscience Johns Hopkins University School of Medicine Department of Pediatrics Johns Hopkins University School of Medicine Department of Physical Medicine and Rehabilitation Johns Hopkins University School of Medicine

The Food and Drug Administration(FDA) has approved two mechanismbased treatments for tuberous sclero-sis complex(TSC)-everolimus and vigabatrin. However, these treatments have not been systematically studied in individuals with TSC and severe autism. The aim of this review is to identify the clinical features of severe autism in TSC, applicable preclinical models, and potential barriers that may warrant strategic planning in the design phase of clinical trial development. A comprehensive search strategy was formed and searched across Pub Med, Embase and SCOPUS from their inception to 2/21/12, 3/16/12, and 3/12/12 respectively. After the final search date, relevant, updated articles were selected from Pub Med abstracts generated electronically and emailed daily from Pub Med. The references of selected articles were searched, and relevant articles were selected. A search of clinicaltrials.gov was completed using the search term "TSC" and "tuberous sclerosis complex". autism has been reported in as many as 60% of individuals with TSC; however, review of the literature revealed few data to support clear classification of the severity of autism in TSC. Variability was identified in the diagnostic approach, assessment of cognition, and functional outcome among the reviewed studies and case reports. Objective outcome measures were not used in many early studies; however, diffusion tensor imaging of white matter, neurophysiologic variability in infantile spasms, and cortical tuber subcategories were examined in recent studies and may be useful for objective classification of TSC in future studies. Mechanism-based treatments for TSC are currently available. However, this literature review revealed two potential barriers to successful design and implementation of clinical trials in individuals with severe autism-an unclear definition of the population and lack of validated outcome measures. Recent studies of objective outcome measures in TSC and further study of applicable preclinical models present an opportunity to overc

关键词： autism Self-injury Aggression Tuberous sclerosis complex Intellectual disability

Culturally adapted pictorial screening tool for autism spectrum disorder:A new approach

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World Journal of Clinical Pediatrics 2017年第1期6卷 45-51页

作者： Hemamali Perera Kamal Chandima Jeewandara Sudarshi Seneviratne Chandima Guruge Department of Psychological Medicine Faculty of MedicineUniversity of Colombo and Lady Ridgeway Hospital for Children Department of Family Medicine Faculty of Medical SciencesUniversity of Sri Jayawardenapura National Hospital of Sri Lanka

AIM To assess the performance of a newly designed,culturally adapted screening tool for autism spectrum disorder(ASD).METHODS Items for the screening tool were modeled from already documented checklists and diagnostic criteria for ASD.Each item in text was paired with a photograph that illustrated the written content,which was in the 2 main local languages.The final product had 21 items and was named the pictorial autism assessment schedule(PAAS).Performance of PAAS was tested on a clinical sample of 18-48 mo old children,diagnosis na?ve,presenting with developmental deficits.Mothers completed PAAS checklist.Based on clinical diagnosis,which was taken as the gold standard,children were later grouped into ASD(Group 1) and non-ASD developmental disorders(Group 2).Mothers of a control sample of typically developing children also completed PAAS(Group 3).RESULTS A total of 105 children(Group 1-45,Group 2-30,Group 3-30) participated in the study.Mean age of Group 1 and Group 2 were 36 and 40 mo respectively.Majority were male in all 3 groups.Performance of PAAS in discriminating between ASD and non-ASD developmental disorders was sensitivity 88.8%,specificity 60.7%,positive predictive value(PPV) 78.4%,negative predictive value(NPV) 77.2%,likelihood ratio(LR+) 2.26,and LR-0.18.Performance of PAAS in discriminating between ASD and typical development was sensitivity 88.0%,specificity 93.3%,PPV 95.2%,NPV 84.0%,LR+ 13.3 and LR- 0.12.The results indicated that that a positive result from PAAS was 2.26 times more likely to be found in a child with ASD than in a child with non-ASD developmental disorder.A positive result from PAAS was 13.3 times more likely to be found in a child with ASD than in a child with typical development.CONCLUSION PAAS is an effective tool in screening for ASD.Further study is indicated to evaluate the feasibility of using this instrument for community screening for ASD.

关键词： autism spectrum disorder Screening tool Culture Ethnicity Parent self-assessment Pictorial

Transition from early intervention program to primary school in children with autism spectrum disorder

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World Journal of Clinical Pediatrics 2017年第4期6卷 169-175页

作者： Valsamma Eapen Rachel Grove Elizabeth Aylward Annette V Joosten Scott I Miller Gerdamari Van Der Watt Kathryn Fordyce Cheryl Dissanayake Jacqueline Maya Madonna Tucker Antonia DeBlasio Academic Unit of Child Psychiatry South West Sydney (AUCS)ICAMHSMental Health CentreL1Liverpool Hospital School of Psychiatry Uni-versity of New South Wales Cooperative Research Centre for Living with autism (autism CRC) KU Marcia Burgess autism Specific Early Learning and Care Centre School of Occupational Therapy and Social Work Curtin University Western Australia autism Specific Early Learning and Care Centre autism Association of Western Australia St Giles Society North West Tasmania autism Specific Early Learning and Care Centre La Trobe University AEIOU Foundation Anglicare SA Daphne St autism Specific Early Learning and Care Centre

AIM To evaluate the characteristics that are associated with successful transition to school outcomes in preschool aged children with autism.METHODS Twenty-one participants transitioning from an early intervention program were assessed at two time points; at the end of their preschool placement and approximately 5 mo later following their transition to school. Child characteristics were assessed using the Mullen Scales of Early Learning, Vineland Adaptive Behaviour Scales, Social Communication Questionnaire and the Repetitive Behaviour Scale. Transition outcomes were assessed using Teacher Rating Scale of School Adjustment and the Social Skills Improvement System Rating Scales to provide an understanding of each child's school adjustment. The relationship between child characteristics and school outcomes was evaluated. RESULTS Cognitive ability and adaptive behaviour were shown to be associated with successful transition to school outcomes including participation in the classroom and being comfortable with the classroom teacher. These factors were also associated with social skills in the classroom including assertiveness and engagement. CONCLUSION Supporting children on the spectrum in the domains of adaptive behaviour and cognitive ability, including language skills, is important for a successful transition to school. Providing the appropriate support within structured transition programs will assist children on the spectrum with this important transition, allowing them to maximise their learning and behavioural potential.

关键词： autism spectrum disorder School transition Primary school Outcomes