Amelioration of social isolation-triggered onset of early Alzheimer%26apos;s disease-related cognitive deficit by N-acetylcysteine in a transgenic mouse model

作者：Hsiao Ya Hsin; Kuo Jinn Rung; Chen Shun Hua; Gean Po Wu^*

来源：Neurobiology of Disease, 2012, 45(3): 1111-1120.

DOI：10.1016/j.nbd.2011.12.031

• Social isolation
• Amyloid-beta peptide
• Long-term potentiation
• Learning and memory
• Alzheimer%26apos
• s disease
• N-acetylcysteine

Epidemiological study reveals that socially isolated persons have increased risk of developing Alzheimer%26apos;s disease (AD). Whether this risk arises from an oxidative stress is unclear. Here we show that N-acetylcysteine (NAC), an anti-oxidant, is capable of preventing social isolation-induced accelerated impairment of contextual fear memory and rundown of hippocampal LTP in 3-month old APP/PS1 mice. Increased hippocampal levels of gamma-secretase activity, A beta-40 and A beta-42 seen in the isolated APP/PS1 mice were reduced by chronic treatment of NAC. In addition, social isolation-induced increase in calpain activity and p25/p35 ratio concomitant with decrease in membrane-associated p35 and p35/Cdk5 activity was normalized by NAC. NAC pretreatment also reversed isolation-induced decrease in GluR1 Ser831 phosphorylation, surface expression of AMPARs and p35-GluR1-CaMKII interactions. These results suggest that NAC decreases gamma-secretase activity resulting in the attenuation of A beta production, calpain activity and conversion of p35 to p25 which stabilized p35-GluR1-CaMKII interactions and restored GluR1 and GluR2 surface expression. Our results indicate that NAC is effective in mouse models of AD and has translation potential for the human disorder.

• 出版日期2012-3