Rambousek Lukas, Kleteckova Lenka, Kubesova Anna, Jirak Daniel, Vales Karel, Fritschy Jean-Marc
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.
2nd Faculty of Medicine, Charles University, Prague, Czech Republic; Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
Neuropharmacology. 2016 Jun;105:594-606. doi: 10.1016/j.neuropharm.2016.02.035. Epub 2016 Feb 27.
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.
用谷氨酸或其他强效激动剂（如NMDA）过度刺激NMDA受体会导致兴奋性毒性和神经损伤。在本研究中，我们旨在深入了解脑兴奋性毒性损伤的动物模型；向海马结构单侧单次注入低剂量的NMDA。注入NMDA会在注射部位附近诱发慢性局灶性神经变性。该损伤伴有严重且进行性的神经炎症，主要影响主神经元，而GABA能中间神经元则未受影响。此外，单侧损伤并未导致空间学习能力出现显著损害。最后，NMDA受体的GluN1和GluN2B亚基在注入NMDA后3天内显著上调，而损伤后30天GABAA α5亚基下调。综上所述，向海马结构单次注入NMDA代表了一种兴奋性毒性诱导的主神经元慢性神经变性的动物模型，伴有严重神经炎症以及NMDA和GABAA受体亚基特异性变化。
