Dysregulation of fragile × mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study
Open accessAbstract
BACKGROUND: Fragile × syndrome is caused by loss of function of the fragile × mental retardation 1 (FMR1) gene and shares multiple phenotypes with autism. We have previously found reduced expression of the protein product of FMR1 (FMRP) in vermis of adults with autism. METHODS: In the current study, we have investigated levels of FMRP in the superior frontal cortex of people with autism and matched controls using Western blot analysis. Because FMRP regulates the translation of multiple genes, we also measured protein levels for downstream molecules metabotropic glutamate receptor 5 (mGluR5) and γ-aminobutyric acid (GABA) A receptor β3 (GABRβ3), as well as glial fibrillary acidic protein (GFAP). RESULTS: We observed significantly reduced levels of protein for FMRP in adults with autism, significantly increased levels of protein for mGluR5 in children with autism and significantly increased levels of GFAP in adults and children with autism. We found no change in expression of GABRβ3. Our results for FMRP, mGluR5 and GFAP confirm our previous work in the cerebellar vermis of people with autism. CONCLUSION: These changes may be responsible for cognitive deficits and seizure disorder in people with autism.
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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 [123]
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- Authors
- Fatemi, S. H., & Folsom, T. D.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Fatemi, S Hossein
- ORCID
- Fatemi, S Hossein
- Venue
- Molecular Autism
- Published
- 2011
- Volume
- 2
- Issue
- 1
- Pages
- 6
- ISSN
- 2040-2392 (ISSN-L)
- PMC
- PMC3488976
- OpenAlex
- W2105523866
- Cited by
- 84
- References
- 62
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 9 · 2023: 1 · 2022: 8 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 10 · 2015: 12 · 2014: 8 · 2013: 13 · 2012: 5
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Autism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Parkinson Foundation
- Parkinsonfonden
- 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, FMRP, metabotropic glutamate receptor 5, GABA-A receptor beta3 subunit, glial fibrillary acidic protein, superior frontal cortex, postmortem brain, FMR1 gene, translational regulation, cognitive impairment, epilepsy
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