NMDA receptor dysfunction in autism spectrum disorders
Abstract
Abnormalities and imbalances in neuronal excitatory and inhibitory synapses have been implicated in diverse neuropsychiatric disorders including autism spectrum disorders (ASDs). Increasing evidence indicates that dysfunction of NMDA receptors (NMDARs) at excitatory synapses is associated with ASDs. In support of this, human ASD-associated genetic variations are found in genes encoding NMDAR subunits. Pharmacological enhancement or suppression of NMDAR function ameliorates ASD symptoms in humans. Animal models of ASD display bidirectional NMDAR dysfunction, and correcting this deficit rescues ASD-like behaviors. These findings suggest that deviation of NMDAR function in either direction contributes to the development of ASDs, and that correcting NMDAR dysfunction has therapeutic potential for ASDs.
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GluN2B is particularly critical for social behaviors in animal models.
“Variations in the gene encoding GluN2B have been frequently identified in neuropsychiatric disorders 62, 63, and studies on animal models have shown that GluN2B is particularly critical for social behaviors 61, 64, 65.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [61]
Normalization of NMDAR function ameliorates core symptoms in a number of ASD animal models.
“These results support the view that normalization of NMDAR function, which show effects for amelioration of core symptoms in a number of ASD animal models, is a promising therapeutic strategy for the disease 61.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [61]
NMDARs are substantially involved in autism spectrum disorder.
“consistent with the significant involvement of NMDARs in ASD [101–103].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [103]
NMDAR hypofunction in the prefrontal cortex is a core mechanism underlying phenotypes linked to 16p11.2 deletion.
“This study suggests NMDAR hypofunction in PFC as a core mechanism in 16p11.2 deletion-linked phenotypes, consistent with the significant involvement of NMDARs in ASD [101–103].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [103]
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- Authors
- Lee, E.-J., Choi, S. Y., & Kim, E.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Corresponding author
- Kim, Eunjoon
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 20
- Pages
- 8-13
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2015029726
- Cited by
- 192
- References
- 50
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 13 · 2023: 9 · 2022: 24 · 2021: 12 · 2020: 22 · 2019: 18 · 2018: 23 · 2017: 17 · 2016: 22 · 2015: 6 · 2012: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institute for Basic Science
- 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
- NMDA receptor dysfunction, autism spectrum disorder, excitatory synapses, excitation-inhibition balance, NMDA receptor subunits, animal models of autism, NMDA receptor modulation, therapeutic potential
- MeSH terms
- Animals, Child Development Disorders, Pervasive, Disease Models, Animal, Humans, Synapses, Genetic Variation, Receptors, N-Methyl-D-Aspartate
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