Metabotropic Glutamate Receptor 5 Upregulation in Children with Autism is Associated with Underexpression of Both Fragile X Mental Retardation Protein and GABAA Receptor Beta 3 in Adults with Autism
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Recent work has demonstrated the impact of dysfunction of the GABAergic signaling system in brain and the resultant behavioral pathologies in subjects with autism. In animal models, altered expression of Fragile X mental retardation protein (FMRP) has been linked to downregulation of GABA receptors. Interestingly, the autistic phenotype is also observed in individuals with Fragile X syndrome. This study was undertaken to test previous theories relating abnormalities in levels of FMRP to GABA A receptor underexpression. We observed a significant reduction in levels of FMRP in the vermis of adults with autism. Additionally, we found that levels of metabotropic glutamate receptor 5 (mGluR5) protein were significantly increased in vermis of children with autism versus age and postmortem interval matched controls. There was also a significant decrease in level of GABA A receptor beta 3 (GABRβ3) protein in vermis of adult subjects with autism. Finally, we found significant increases in glial fibrillary acidic protein in vermis of both children and adults with autism when compared with controls. Taken together, our results provide further evidence that altered FMRP expression and increased mGluR5 protein production potentially lead to altered expression of GABA A receptors. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
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Postmortem studies show reduced FMRP in cerebella and frontal cortices of autistic subjects without FXS mutations.
“Recent postmortem work has shown reductions in FMRP in cerebella and frontal cortices of subjects with autism who do not carry a mutation for FXS [123, 128].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [128]
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- Authors
- Fatemi, S. H., Folsom, T. D., Kneeland, R. E., & Liesch, S. B.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Fatemi, S. Hossein
- ORCID
- Fatemi, S. Hossein
- Venue
- The Anatomical Record
- Publisher
- Wiley
- Published
- 2011-09-08
- Volume
- 294
- Issue
- 10
- Pages
- 1635-1645
- ISSN
- 1932-8486 (ISSN-L)
- 1932-8494
- PMC
- PMC3177171
- OpenAlex
- W2015606490
- Cited by
- 137
- References
- 83
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 10 · 2022: 10 · 2021: 8 · 2020: 9 · 2019: 5 · 2018: 13 · 2017: 3 · 2016: 10 · 2015: 13 · 2014: 19 · 2013: 13 · 2012: 15
- FWCI
- 9.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Anatomical Record (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Parkinson Foundation
- Parkinson's Foundation
- National Institute of Mental Health (R24MH068855)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD052074)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, metabotropic glutamate receptor 5, FMRP, GABAergic neurotransmission, cerebellar vermis, glial fibrillary acidic protein, postmortem brain, children and adults with autism, fragile X syndrome
- MeSH terms
- Adolescent, Adult, Age Factors, Autistic Disorder, Child, Child, Preschool, Electrophoresis, Polyacrylamide Gel, Female, Humans, Male, Middle Aged, Receptors, GABA-A, Blotting, Western, Receptors, Metabotropic Glutamate, Fragile X Messenger Ribonucleoprotein 1, Young Adult, Receptor, Metabotropic Glutamate 5
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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