colivelin and Cognition-Disorders

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-β protein (Aβ) even at a low concentration. We recently demonstrated that intrahippocampal injection of CLN prevents Aβ25-35-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-month-old 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 Aβ 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 Aβ deposition and alleviation of LTP suppression in the hippocampus, supporting the potential of CLN for the prevention and treatment of AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Analysis of Variance; Animals; Cognition Disorders; Disease Models, Animal; Exploratory Behavior; Hippocampus; Intracellular Signaling Peptides and Proteins; Long-Term Potentiation; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Neuronal Plasticity; Neuroprotective Agents; Patch-Clamp Techniques; Presenilin-1; Recognition, Psychology; Time Factors