ArticleAutism research : official journal of the International Society for Autism Research2009
Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study.
Article in Autism research : official journal of the International Society for Autism Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 4 of them syntheses that pooled it.
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Who cites it
62 citing papers in PubMed, 4 syntheses or guidelines pooled it, 122 citations in OpenAlex.
- Neurometabolite levels in the brains of patients with autism spectrum disorders: A meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501).Molecular psychiatry · 2023Pooled it
- Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies.Human brain mapping · 2016Pooled it
- Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies.Journal of autism and developmental disorders · 2016Pooled it
- Blood Glutamate Levels in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.PloS one · 2016Pooled it
- Baclofen as an adjuvant therapy for autism: a randomized, double-blind, placebo-controlled trial.European child & adolescent psychiatry · 2019Trial
- Cerebellar Abnormalities: A Component of Autism Pathophysiology.Medicina (Kaunas, Lithuania) · 2026Review
- Stem Cell Therapy and Models for Autism Spectrum Disorder: Insights and Research.Current neuropharmacology · 2026Review
- Dopamine Dysregulation in Reward and Autism Spectrum Disorder.Brain sciences · 2024Review
- Cerebellum Lecture: the Cerebellar Nuclei-Core of the Cerebellum.Cerebellum (London, England) · 2024Review
- Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder.Current neuropharmacology · 2024Review
- The Cerebellum-Ventral Tegmental Area Microcircuit and Its Implications for Autism Spectrum Disorder: A Narrative Review.Neuropsychiatric disease and treatment · 2024Review
- Relationships between GABA, glutamate, and GABA/glutamate and social and olfactory processing in children with autism spectrum disorder.Psychiatry research. Neuroimaging · 2023Article
- A neuro-computational social learning framework to facilitate transdiagnostic classification and treatment across psychiatric disorders.Neuroscience and biobehavioral reviews · 2023Review
- A bibliometric analysis of global research status and trends in neuromodulation techniques in the treatment of autism spectrum disorder.BMC psychiatry · 2023Article
- Structural neuroimaging phenotypes and associated molecular and genomic underpinnings in autism: a review.Frontiers in neuroscience · 2023Review
- Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2022Review
- Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission.International journal of molecular sciences · 2022Review
- The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models.International journal of molecular sciences · 2022Review
- Structure, Function, and Genetics of the Cerebellum in Autism.Journal of psychiatry and brain science · 2022Article
- Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The laterally positioned dentate nuclei lie in a key position in the cerebellum to receive input from Purkinje cells in the lateral cerebellar hemisphere participating in both motor and cognitive functions. Although neuropathology of the four cerebellar nuclei using Nissl staining has been qualitatively reported in children and adults with autism, surprisingly the dentate nuclei appeared less affected despite reported reductions in Purkinje cells in the posterolateral cerebellar hemisphere. To determine any underlying abnormalities in the critically important GABAergic system, the rate-limiting GABA synthesizing enzyme, glutamic acid decarboxylase (GAD) type 65 was measured via in situ hybridization histochemistry in dentate somata. GAD65 mRNA labeling revealed two distinct subpopulations of neurons in adult control and autism postmortem brains: small-sized cells (about 10-12 microm in diameter, presumed interneurons) and larger-sized neurons (about 18-20 microm in diameter, likely feedback to inferior olivary neurons). A mean 51% reduction in GAD65 mRNA levels was found in the larger labeled cells in the autistic group compared with the control group (P=0.009; independent t-test) but not in the smaller cell subpopulation. This suggests a disturbance in the intrinsic cerebellar circuitry in the autism group potentially interfering with the synchronous firing of inferior olivary neurons, and the timing of Purkinje cell firing and inputs to the dentate nuclei. Disturbances in critical neural substrates within these key circuits could disrupt afferents to motor and/or cognitive cerebral association areas in the autistic brain likely contributing to the marked behavioral consequences characteristic of autism.
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