GLP-1 analogue CJC-1131 prevents amyloid beta protein-induced impirments of spatial memory and synaptic plasticity in rats

摘要

Although amyloid 13 protein (A(3) has been recognized as one of the main pathological characteristics in the brain of Alzheimer's disease (AD), the effective strategies against A beta neurotoxicity are still deficient up to now. Glucagon-like peptide 1 (GLP-1), a natural gut hormone, was found to be effective in modulating insulin signaling and neural protection, but short half-life limited its clinical application in AD treatment. CJC-1131, a newly designed GLP-1 analogue with very longer half-life, has shown good effectiveness in the treatment of type 2 diabetes mellitus (T2DM). However, it is unclear whether CJC-1131 could alleviate A beta-induced neurotoxicity in cognitive behavior and electrophysiological property. The present study investigated the effects of CJC-1131 on the A beta-induced impairments in spatial memory and synaptic plasticity of rats by using Morris water maze test and in vivo field potential recording. The results showed that A beta 1-42-induced increase in the escape latency of rats in hidden platform test and decrease in swimming time percent in target quadrant were effectively reversed by CJC-1131 pretreatment. Further, CJC-1131 prevented against A beta 1-42-induced suppression of hippocampal long term potentiation (LTP). In addition, A beta 1-42 injection resulted in a significant decrease of p-PKA in the hippocampus, which was effectively prevented by CJC-1131 treatment. These results indicated that CJC-1131 protected the cognitive function and synaptic plasticity of rats against A beta-induced impairments, suggesting that GLP-1 analogue CJC-1131 might be potentially beneficial to the prevention and treatment of AD, especially those with T2DM or blood glucose abnormality. (C) 2017 Elsevier B.V. All rights reserved.