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Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABAA receptor subunits
L. Rambousek, L. Kleteckova, A. Kubesova, D. Jirak, K. Vales, JM. Fritschy,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
- MeSH
- bludiště - učení účinky léků fyziologie MeSH
- degenerace nervu diagnostické zobrazování metabolismus patologie MeSH
- funkční lateralita MeSH
- hipokampus diagnostické zobrazování účinky léků metabolismus patologie MeSH
- modely nemocí na zvířatech MeSH
- N-methylaspartát aplikace a dávkování toxicita MeSH
- neurodegenerativní nemoci diagnostické zobrazování metabolismus patologie MeSH
- neuroimunomodulace fyziologie MeSH
- neurony účinky léků metabolismus patologie MeSH
- potkani Long-Evans MeSH
- receptory GABA-A metabolismus MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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.
2nd Faculty of Medicine Charles University Prague Czech Republic
Institute for Clinical and Experimental Medicine Prague Czech Republic
Institute of Physiology Academy of Sciences Prague Czech Republic
National Institute of Mental Health Klecany Czech Republic
Neuroscience Center Zurich University and ETH Zurich Zurich Switzerland
Citace poskytuje Crossref.org
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- $a 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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