GLP-1 analogue CJC-1131 prevents amyloid β protein-induced impirments of spatial memory and synaptic plasticity in rats.
Although amyloid β protein (Aβ) has been recognized as one of the main pathological characteristics in the brain of Alzheimer's disease (AD), the effective strategies against Aβ 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 Aβ-induced neurotoxicity in cognitive behavior and electrophysiological property. The present study investigated the effects of CJC-1131 on the Aβ-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 Aβ1-42-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 Aβ1-42-induced suppression of hippocampal long term potentiation (LTP). In addition, Aβ1-42 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 Aβ-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.
Department of Rheumatology, The Second Hospital of Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
Sheng-Xiao
SX
Zhang
Department of Microbiology and Immunology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
Hong-Yan
HY
Cai
Department of Rheumatology, The Second Hospital of Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
Xiao-Wen
XW
Ma
Department of Physiology and National Key Discipline of Physiology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
Li
L
Yuan
Department of Physiology and National Key Discipline of Physiology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
Jun
J
Zhang
Department of Physiology and National Key Discipline of Physiology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
Zhao-Jun
ZJ
Wang
Department of Rheumatology, The Second Hospital of Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
Yu-Feng
YF
Li
Department of Physiology and National Key Discipline of Physiology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China. Electronic address: jinshunqi2009@163.com.
Jin-Shun
JS
Qi
D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D055724:Electrophysiological Phenomena; D052216:Glucagon-Like Peptide 1 / Q000032:analysis*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008301:Maleimides / Q000008:administration & dosage / Q000494:pharmacology*; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects*
D016229:Amyloid beta-Peptides; C473712:CJC 1131; D008301:Maleimides; D018696:Neuroprotective Agents; D010455:Peptides; D052216:Glucagon-Like Peptide 1
Amyloid β protein; CJC-1131; Long-term potentiation; Morris water maze; Spatial memory; Synaptic plasticity