α-lipoic acid attenuates apoptosis and accompany with autophagy in chronic hypoperfusion animal models

[Speaker] Ji-Hye Park:1,3
[Co-author] Yong Cheon Na:2, Chang Yeob Han:3, Seong Bin Park:4, Mi Jeong Han:3, Seoul Lee:1,3
1:Wonkwang Brain Reserch Institute, Korea, 2:Wonkwang Medical Institue, Korea, 3:Department of Pharmacology, Wonkwang University School of Medicine, Korea, 4:Korea Human Resource Development Institute For Health & Welfare, Korea

Vascular dementia (VaD) is the second most common cause of dementing symptoms after Alzheimer's disease. Bilateral common carotid artery stenosis (BCCAS) has been established a VaD model in mice. The α-lipoic acid (α-LA) is known as an antioxidant which eliminate many reactive oxygen species. So many clinical and basic researches were attempted to determine whether α-LA can recovery of cognitive function under the neurodegenerative conditions but an action mechanism is still not unclear. 8-weeks old c57BL/6 mice were subjected and they were divided into the sham-operation group (SHAM), the BCCAS group (BCCAS) and the BCCAS treatment with α-LA (BCCAS+α-LA; 100 mg/kg, daily IP injection). Subjects were given surgical operation and administered vehicle and α-LA up to 30 consecutive days. On day 28, we evaluated a cognitive and behavioral functions via Morris water maze task for 7 days. After the behavior test, subjects were sacrificed to investigate an action mechanism. In Morris water maze test, the BCCAS group reveal a decreased in cognitive function than SHAM group, but the BCCAS+α-LA group show similar results compare to the SHAM group. The removed brains were sectioned and performed Western blot to examine molecular mechanisms of action. PSD95, VAMP8, SNAP29, and P62 proteins were decreased in the BCCAS group than the SHAM group, however the BCCAS+ α-LA tend to be increased PSD95, VAMP8, LC3B and decreased SNAP29 compare with the BCCAS group. And P-RAPTOR, P-mTOR and PARP increased in BCCAS group than the SHAM group but this is attenuate in the BCCAS+ α-LA group. These results indicated that chronic cerebral blood flow hypoperfusion could make a cognitive dysfunction such as vascular dementing. Interestingly, a chronic treatment with α-LA might be protective effects in this BCCAS mice model accompany with a neural protection and an autophagy mechanism. These results suggested that autophagy induction by α-LA can give an effect of neuronal survival in vascular dementia mimic animal studies. This research supported by National Research Foundation of Korea in 2017R1A6A3A11033019
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