Glutamate receptor dysfunction and drug targets across models of autism spectrum disorders
Open accessAbstract
There is strong evidence that metabotropic and ionotropic glutamate receptors are affected in autism spectrum disorders (ASD), but there are few candidate genes indicating involvement of these receptors. This suggests that glutamate receptor dysregulation may primarily be involved in the expression of ASD, but is an uncommon etiology. Directly implicated in models of fragile-X with ASD phenotypes is metabotropic glutamate receptor type 5 (mGluR5), which appears to be an effective pharmacologic target in a number of models of ASD. The review of other ASD models demonstrates that there is also evidence of a role for kainate, NMDA, and AMPA receptors in the neuropathophysiology of ASD, though the relationship between dysfunction in those receptors and ASD-associated phenotypes is not well understood. Current models indicate a way forward to delineate the role of glutamate receptors in ASD. Further development of preclinical models focusing on glutamate receptors may provide tools to target a clinically important subset of ASD symptoms.
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The therapeutic armamentarium aimed at autism derives specificity from neurotransmitter systems broadly, or receptor subtypes like mGluR5, known or believed likely to influence development or expression of core or related autism symptoms.
“Indeed, to the extent that the therapeutic armamentarium is aimed in a specific way at autism, the specificity derives from neurotransmitter systems broadly, or in some cases receptor subtypes, such as metabotropic glutamate receptors like mGluR5 [255], that are known or believed likely to influence the development or expression of core or related autism symptoms.”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [255]
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- Authors
- Carlson, G. C.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Carlson, Greg C.
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 100
- Issue
- 4
- Pages
- 850-854
- ISSN
- 0091-3057 (ISSN-L)
- PMC
- PMC3132310
- OpenAlex
- W2054063927
- Cited by
- 102
- References
- 82
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 16 · 2021: 5 · 2020: 9 · 2019: 2 · 2018: 9 · 2017: 2 · 2016: 2 · 2015: 10 · 2014: 16 · 2013: 10 · 2012: 9
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD062577, HD062577-02)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, glutamate receptors, metabotropic glutamate receptor 5, mGluR5, fragile X syndrome, ionotropic glutamate receptors, kainate receptors, NMDA receptor, AMPA receptors, preclinical animal models, therapeutic target, neuropathophysiology
- MeSH terms
- Child, Child Development Disorders, Pervasive, Humans, Receptors, Glutamate
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