GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia
Involvement of the glutamate system, particularly N-methyl-D-aspartate (NMDA) receptor hypofunction, has long been postulated to be part of the pathophysiology of schizophrenia. An important development is provided by recent data that strongly implicate <i>GRIN2A</i>, the gene encoding t...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2023
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| _version_ | 1797112769120567296 |
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| author | Harrison, PJ Bannerman, DM |
| author_facet | Harrison, PJ Bannerman, DM |
| author_sort | Harrison, PJ |
| collection | OXFORD |
| description | Involvement of the glutamate system, particularly N-methyl-D-aspartate (NMDA) receptor hypofunction, has long been postulated to be part of the pathophysiology of schizophrenia. An important development is provided by recent data that strongly implicate <i>GRIN2A</i>, the gene encoding the NR2A (GluN2A) NMDA receptor subunit, in the aetiology of the disorder. Rare variants and common variants are both robustly associated with genetic risk for schizophrenia. Some of the rare variants are point mutations likely affecting channel function, but most are predicted to cause protein truncation and thence result, like the common variants, in reduced gene expression. We review the genomic evidence, and the findings from <i>Grin2a</i> mutant mice and other models which give clues as to the likely phenotypic impacts of <i>GRIN2A</i> genetic variation. We suggest that one consequence of NR2A dysfunction is impairment in a form of hippocampal synaptic plasticity, producing deficits in short-term habituation and thence elevated and dysregulated levels of attention, a phenotype of relevance to schizophrenia and its cognitive aspects. |
| first_indexed | 2024-03-07T08:28:37Z |
| format | Journal article |
| id | oxford-uuid:0a44f670-5b28-4f30-afa4-384a6e0aafae |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:28:37Z |
| publishDate | 2023 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:0a44f670-5b28-4f30-afa4-384a6e0aafae2024-03-05T11:10:35ZGRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophreniaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0a44f670-5b28-4f30-afa4-384a6e0aafaeEnglishSymplectic ElementsSpringer Nature2023Harrison, PJBannerman, DMInvolvement of the glutamate system, particularly N-methyl-D-aspartate (NMDA) receptor hypofunction, has long been postulated to be part of the pathophysiology of schizophrenia. An important development is provided by recent data that strongly implicate <i>GRIN2A</i>, the gene encoding the NR2A (GluN2A) NMDA receptor subunit, in the aetiology of the disorder. Rare variants and common variants are both robustly associated with genetic risk for schizophrenia. Some of the rare variants are point mutations likely affecting channel function, but most are predicted to cause protein truncation and thence result, like the common variants, in reduced gene expression. We review the genomic evidence, and the findings from <i>Grin2a</i> mutant mice and other models which give clues as to the likely phenotypic impacts of <i>GRIN2A</i> genetic variation. We suggest that one consequence of NR2A dysfunction is impairment in a form of hippocampal synaptic plasticity, producing deficits in short-term habituation and thence elevated and dysregulated levels of attention, a phenotype of relevance to schizophrenia and its cognitive aspects. |
| spellingShingle | Harrison, PJ Bannerman, DM GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia |
| title | GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia |
| title_full | GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia |
| title_fullStr | GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia |
| title_full_unstemmed | GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia |
| title_short | GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia |
| title_sort | grin2a nr2a a gene contributing to glutamatergic involvement in schizophrenia |
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