期刊
BRAIN RESEARCH
卷 1215, 期 -, 页码 208-217出版社
ELSEVIER
DOI: 10.1016/j.brainres.2008.04.001
关键词
memantine; mitochondrial dysfunction; neurodegeneration; neuroprotection; rotenone; oxidative stress; energy metabolism
资金
- NIMH NIH HHS [MH65728, T32 MH065728-06, T32 MH065728] Funding Source: Medline
This is the first report of the in vivo effectiveness of memantine as a neuroprotective agent against rotenone-induced retinal toxicity. We tested the hypothesis that uncompetitive NMDAR blockade with memantine prevents mitochondrial dysfunction-related neurodegeneration in vivo, using a mouse model of retinal ganglion cell layer (GCL) degeneration induced by rotenone, a mitochondrial complex I inhibitor. Rotenone induced an increase in cell death and oxidative stress in GCL compared to controls, and these changes were prevented by the co-administration of memantine. The neurotoxic effect of rotenone was also reflected as a decrease in total cell density in GCL and GCL+nerve fiber layer thickness. These changes were also prevented by co-administration of memantine in a dose-dependent manner. In addition, memantine induced an increase in long-term retinal energy metabolic capacity. The results suggest that NMDAR activation contributes to cell death induced by mitochondrial dysfunction and that uncompetitive NMDAR blockade may be used as a neuroprotective strategy against mitochondrial dysfunction in neurodegenerative diseases. (c) 2008 Elsevier B.V. All rights reserved.
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