Five weeks after bilateral olfactory bulbectomy (OBX) NMRI mice displayed considerable impairment of spatial memory and increased level of beta-amyloid in the brain and seems to be appropriate model of sporadic Alzheimer’s disease [1]. We was investigated the resting and phosphorylating respiratory rates and respiration control ratio as well as membrane potential and activity of respiratory complexes in mitochondria isolated from the neocortex and hippocampus. We have found impairments of mitochondrial oxygen metabolism and inhibition of the respiratory complexes in mitochondria from the neocortex and hippocampus in OBX mice. Obtained data was shown to be significantly decrease the rate of the respiratory chain functioning that could be result from the reduced activities of the electron transport chain complexes, namely NADH: ubiquinone oxidoreductase (complex I) and cytochrome c oxidase (complex IV). Synthetic peptides corresponding to nonstructural region of the extracellular domain of Receptor for Advanced Glycation End Products (RAGE) known as amyloid-β receptor have been examined as therapeutic substances under intranasal administration. The treatment of mice with fragment RAGE (60-76) for 3 weeks was shown an improving the spatial memory in OBX mice with simultaneous reactivation of impaired electron transport chain complexes I and IV in cortical and hippocampal mitochondria, whereas peptide RAGE (60-62) did not show such positive effect.
lzheimer’s disease, mitochondria, respiratory complexes, RAGE, synthetic peptides
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