Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABAA receptor subunits
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26930443
DOI
10.1016/j.neuropharm.2016.02.035
PII: S0028-3908(16)30070-3
Knihovny.cz E-resources
- Keywords
- Carousel maze, Excitotoxicity, GABA A receptor, Hippocampus, Interneurons, NMDA receptor, Neurodegeneration, Neuroinflammation, Spatial learning,
- MeSH
- Maze Learning drug effects physiology MeSH
- Nerve Degeneration diagnostic imaging metabolism pathology MeSH
- Functional Laterality MeSH
- Hippocampus diagnostic imaging drug effects metabolism pathology MeSH
- Disease Models, Animal MeSH
- N-Methylaspartate administration & dosage toxicity MeSH
- Neurodegenerative Diseases diagnostic imaging metabolism pathology MeSH
- Neuroimmunomodulation physiology MeSH
- Neurons drug effects metabolism pathology MeSH
- Rats, Long-Evans MeSH
- Receptors, GABA-A metabolism MeSH
- Receptors, N-Methyl-D-Aspartate metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Gabra5 protein, rat MeSH Browser
- N-Methylaspartate MeSH
- NR1 NMDA receptor MeSH Browser
- NR2B NMDA receptor MeSH Browser
- Receptors, GABA-A MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
Excessive stimulation of NMDA receptors with glutamate or other potent agonists such as NMDA leads to excitotoxicity and neural injury. In this study, we aimed to provide insight into an animal model of brain excitotoxic damage; single unilateral infusion of NMDA at mild dose into the hippocampal formation. NMDA infusion induced chronic, focal neurodegeneration in the proximity of the injection site. The lesion was accompanied by severe and progressive neuroinflammation and affected preferentially principal neurons while sparing GABAergic interneurons. Furthermore, the unilateral lesion did not cause significant impairment of spatial learning abilities. Finally, GluN1 and GluN2B subunits of NMDA receptor were significantly upregulated up to 3 days after the NMDA infusion, while GABAA α5 subunit was downregulated at 30 days after the lesion. Taken together, a single infusion of NMDA into the hippocampal formation represents an animal model of excitotoxicity-induced chronic neurodegeneration of principal neurons accompanied by severe neuroinflammation and subunit specific changes in NMDA and GABAA receptors.
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