title: Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABAA receptor subunits.
abstract: 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.
authors.affiliation: Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; Institute of Physiology, Academy of Sciences, Prague, Czech Republic. Electronic address: rambousek@immunology.uzh.ch.
authors.forename: Lukas
authors.initials: L
authors.lastname: Rambousek
authors.affiliation: 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Kleteckova
authors.affiliation: National Institute of Mental Health, Klecany, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Kubesova
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Institute of Biophysics and Informatics, 1st Medicine Faculty, Charles University, Prague, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jirak
authors.affiliation: Institute of Physiology, Academy of Sciences, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Vales
authors.affiliation: Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Fritschy
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007839:Functional Laterality; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000633:toxicity*; D009410:Nerve Degeneration / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D015213:Neuroimmunomodulation / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: C511535:Gabra5 protein, rat; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate
keywords: Carousel maze; Excitotoxicity; GABA A receptor; Hippocampus; Interneurons; NMDA receptor; Neurodegeneration; Neuroinflammation; Spatial learning