期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 59, 期 3, 页码 1067-1078出版社
IOS PRESS
DOI: 10.3233/JAD-170307
关键词
Amyloid-beta protein; APP/PS1 transgenic mice; colivelin; learning and memory; long-term potentiation
资金
- Fund Program for Sanjin Scholars of Shanxi Province
- National Natural Science Foundation of China [31471080, 31300968]
- Shanxi Scholarship Council of China [2013-054]
- Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province
- Fund for Shanxi Key Subjects Construction
Alzheimer's disease (AD) is the most common cause of dementia, and effective therapeutics are lacking. Colivelin (CLN), a novel, strong humanin derivative, is effective in vitro in preventing cell death induced by AD-causative genes and amyloid-beta protein (A beta) even at a low concentration. We recently demonstrated that intrahippocampal injection of CLN prevents A beta(25-35)-induced deficits in spatial memory and synaptic plasticity in normal rats. Here, we further observed the effects of chronically intranasally (i.n.) administered CLN on cognitive behaviors and pathological hallmarks in 9-monthold APPswe/PS1dE9 (APP/PS1) AD mice using multiple behavioral tests and immunochemistry. The electrophysiological mechanism of CLN neuroprotection was also investigated by recording in vivo hippocampal long-term potentiation (LTP). CLN pretreatment effectively prevented impairments in new object recognition, working memory, and long-term spatial memory and reversed the depression of in vivo hippocampal LTP in APP/PS1 mice. Additionally, chronic application of CLN obviously reduced A beta deposition in the hippocampus in APP/PS1 mice. These results indicate that CLN has strong neuroprotective effects on learning and memory behaviors in APP/PS1 mice and that this behavioral improvement is closely associated with the reduction of A beta deposition and alleviation of LTP suppression in the hippocampus, supporting the potential of CLN for the prevention and treatment of AD.
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