小脳室頂核電気刺激による神経細胞のミトコンドリア機能の強化

抄録

While the electrical stimulation of fastigial nucleus (FN) induces long lasting neuroprotection against focal and global ischemia, the mechanisms remain unknown. FN stimulation may increase the tolerance of the mitochondrial membrane potential (MMP) in the neurons, which could be neuroprotective. To test this hypothesis, we examined the effects of FN stimulation on MMP in the brain slice following an application of mitochondria toxin. In adult rats, FN was electrically stimulated for 1 h, and 3 days later the cortical slices (200 μm-thick) were prepared. The MMP was measured under the epifluorescence microscope using rhodamine 123 (Rh123, 0.1 μM). The changes in fluorescence intensity (FI) of Rh123 in the cortical neurons were analyzed for 15 min with a superfusion of carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP, 10 μM), a mitochondrial uncoupler. In rats without FN stimulation, vehicle alone slightly decreased FI by 7% (to 93 ± 3.1%, n = 12) in 15 min due to photobleaching. Application of FCCP significantly decreased FI by 19% (to 81 ± 4.8%, n = 15), indicating the decrease in MMP. In FN-stimulated rats, FCCP-evoked decrease of MMP was significantly attenuated and was comparable to that observed during vehicle superfusion (to 90 ± 6.0%, n = 19 and 94 ± 2.4%, n = 16, respectively). Data indicate that FN stimulation stabilizes MMP during application of uncoupler. Increased mitochondrial tolerance against depolarization may be a component of the endogenous neuroprotective mechanism. [Jpn J Physiol 55 Suppl:S232 (2005)]