Yan-Li Jia, Su-Juan Sun, Jing-Hong Chen, Qian Jia, Tian-Tian Huo, Li-Fang Chu, Jiang-Tao Bai, Ye-Jing Yu, Xiao-Xin Yan and Jian-Hua Wang Pages 297 - 306 ( 10 )
Mitochondrial dysfunction, oxidative stress and β -amyloid (Aβ) formation are thought to cause neuronal and synaptic degeneration underlying cognitive decline in Alzheimer’s disease (AD). The senescence-accelerated mouse-prone 8 (SAMP8) mice have been used as an animal model for mechanistic and translational research for AD. In the present study we characterized mitochondrial and synaptic alterations in SAMP8 mice relative to SAMR1control mice and explored a protective effect of the small molecule peptide SS31, a cell membrane penetrant antioxidant, on mitochondrial and synaptic protein integrity as well as cognitive performance. Electron microscopic analysis revealed mitochondrial/synaptic deterioration in 10 months-old SAMP8 relative to SAMR1 mice, with the changes in the former rescued following 8 weeks treatment with SS31 (5 mg/kg/day, i.p.). Elevation of Aβ42, mitochondrial fission protein (DLP1, Fis1) and matrix protein cyclophilin D (CypD), and reductions of mitochondrial fusion protein (Mfn2) and synaptic (i.e. synaptophysin, postsynaptic density protein 95 and growth associated protein 43) proteins, were detected in hippocampal lysates in SAMP8 mice relative to SAMR1. The above altered protein expressions in the SAMP8 mouse brain were restored with the SS31 treatment. Moreover, the SS31 treatment rescued learning and memory deficits detected in 10 month-old SAMP8 mice. Together, the findings suggest that this mitochondria-targeting antioxidant peptide may be of potential utility for AD therapy, with its pharmacological efficacy involves lowering of central Aβ levels and protection of mitochondrial homeostasis and synaptic integrity, which may help slow down cognitive decline.
Alzheimer’s disease, amyloid pathology, antioxidants, mice, mitochondria, oxidative stress, synaptic function.
Department of Neurology, Hebei General Hospital, Shijiazhuang, 050051, China.