Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABA(A) receptor subunits

0467410 - FGÚ 2017 RIV NL eng J - Journal Article
Rambousek, Lukáš - Kletečková, Lenka - Kubesová, A. - Jirák, D. - Valeš, Karel - Fritschy, J.M.
Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABA(A) receptor subunits.
Neuropharmacology. Roč. 105, Jun (2016), s. 594-606. ISSN 0028-3908. E-ISSN 1873-7064
R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA14-20613S; GA ČR(CZ) GAP303/12/1464
Institutional support: RVO:67985823
Keywords : excitotoxicity * NMDA receptor * GABA A receptor * hippocampus * neuroinflammation * neurodegeneration * interneurons * spatial learning * carousel maze
Subject RIV: FH - Neurology
Impact factor: 5.012, year: 2016

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 GIuN2B subunits of NMDA receptor were significantly upregulated up to 3 days after the NMDA infusion, while GABA(A) alpha 5 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 GABA(A) receptors.
Permanent Link: http://hdl.handle.net/11104/0265512