Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction
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Significance: We sought to determine whether the diverse hippocampal neuropathology observed in schizophrenia could be recapitulated in an animal model of NMDA receptor (NMDAR) hypofunction. Serine racemase-deficient (SR −/− ) mice, which lack one of the NMDAR coagonists d -serine, display impaired hippocampal plasticity, as well as the morphological, neurochemical, and cognitive abnormalities consistent with what is observed in schizophrenia. Importantly, treatment in adulthood with d -serine reversed the electrophysiological, neurochemical, and cognitive deficits. These results demonstrate that NMDAR hypofunction can reproduce the hippocampal deficits associated with schizophrenia and point to potential interventions for the currently untreatable negative and cognitive symptoms of this disorder.
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Severe NMDAR blockade induces forebrain apoptosis in rats only when administered between the first and third postnatal week.
“Moreover, severe NMDAR blockade induces forebrain apoptosis in rats, but only when administered between the first and third postnatal week 28 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [28]
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- Authors
- Balu, D. T., Li, Y., Puhl, M. D., Benneyworth, M. A., Basu, A. C., Takagi, S., Bolshakov, V. Y., & Coyle, J. T.
- Affiliations
- Harvard University (US)
- Tokyo Medical and Dental University (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-05-31
- Volume
- 110
- Issue
- 26
- Pages
- E2400-9
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3696825
- OpenAlex
- W1964764373
- Cited by
- 217
- References
- 83
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 15 · 2023: 9 · 2022: 18 · 2021: 17 · 2020: 16 · 2019: 15 · 2018: 15 · 2017: 21 · 2016: 26 · 2015: 17 · 2014: 26 · 2013: 6
- FWCI
- 17.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dana-Farber/Harvard Cancer Center (P30 CA 06516, CA06516)
- National Institutes of Health (R01MH05190, P50MH0G0450, CA06516)
- National Institute of Mental Health (R01MH051290, R01MH05190, P50MH0G0450, F32MH090697)
- National Institute on Drug Abuse (T32DA015036)
- National Cancer Institute (P30-CA06516, P30CA006516)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- schizophrenia, NMDA receptor hypofunction, D-serine, hippocampus, dendritic spines, hippocampal volume, long-term potentiation, dentate gyrus granule cells, neuroplasticity
- MeSH terms
- Serine Racemase, Animals, Cognition Disorders, Disease Models, Animal, Humans, Male, Neuronal Plasticity, Risk Factors, Schizophrenia, Serine, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Mice, Knockout, Brain-Derived Neurotrophic Factor, Excitatory Postsynaptic Potentials, Racemases and Epimerases, Receptor, trkB, MicroRNAs, Dendritic Spines, Mice
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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