Journal ArticleDOI
Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications
TLDR
The results indicate that GAD67 mRNA level was reduced by 40% in the autistic group, suggesting that reduced Purkinje cell GABA input to the cerebellar nuclei potentially disrupts Cerebellar output to higher association cortices affecting motor and/or cognitive function.Abstract:
The recent identification of decreased protein levels of glutamate decarboxylase (GAD) 65 and 67 isoforms in the autistic cerebellar tissue raises the possibility that abnormal regulation of GABA production in individual neurons may contribute to the clinical features of autism. Reductions in Purkinje cell number have been widely reported in autism. It is not known whether the GAD changes also occur in Purkinje cells at the level of transcription. Using a novel approach, the present study quantified GAD67 mRNA, the most abundant isoform in Purkinje cells, using in situ hybridization in adult autistic and control cases. The results indicate that GAD67 mRNA level was reduced by 40% in the autistic group (P < 0.0001; two-tailed t test), suggesting that reduced Purkinje cell GABA input to the cerebellar nuclei potentially disrupts cerebellar output to higher association cortices affecting motor and/or cognitive function. These findings may also contribute to the understanding of previous reports of alterations in the GABAergic system in limbic and cerebro-cortical areas contributing to a more widespread pathophysiology in autistic brains.read more
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Neuroanatomy of autism
TL;DR: It is suggested that the heterogeneity of both the core and co-morbid features predicts a heterogeneous pattern of neuropathology in autism, and defined phenotypes in larger samples of children and well-characterized brain tissue will be necessary for clarification of the neuroanatomy of autism.
Journal ArticleDOI
Advancing the understanding of autism disease mechanisms through genetics
TL;DR: Current understanding of the genetic architecture of ASD is reviewed and genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology are integrated.
Journal ArticleDOI
The neuropsychiatry of the cerebellum - insights from the clinic.
TL;DR: The broader role of the cerebellum in the pathogenesis of these neuropsychiatric symptoms is discussed, and the possibility of using cerebellar stimulation to treat psychiatric disorders by enhancing Cerebellar modulation of cognition and emotion is revisited.
Journal ArticleDOI
Consensus Paper: Pathological Role of the Cerebellum in Autism
S. Hossein Fatemi,Kimberly A. Aldinger,Paul Ashwood,Margaret L. Bauman,Charles D. Blaha,Gene J. Blatt,Abha Chauhan,Ved Chauhan,Stephen R. Dager,Price E. Dickson,Annette Estes,Dan Goldowitz,Detlef H. Heck,Thomas L. Kemper,Bryan H. King,Loren A. Martin,Kathleen J. Millen,Guy Mittleman,Matthew W. Mosconi,Antonio M. Persico,John A. Sweeney,Sara Jane Webb,John P. Welsh +22 more
TL;DR: The diversity of opinions regarding the involvement of this important site in the pathology of autism will be observed, and points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, Cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism.
Journal ArticleDOI
Sensory perception in autism
TL;DR: It is argued that sensory traits have important implications for the development of animal and computational models of the condition and how difficulties in sensory processing may relate to the other domains of behaviour that characterize autism.
References
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