Colivelin ameliorates amyloid β peptide-induced impairments in spatial memory, synaptic plasticity, and calcium homeostasis in rats

• Published in: Hippocampus Vol. 25; no. 3; pp. 363 - 372
• Main Authors: Wu, Mei-Na, Zhou, Li-Wei, Wang, Zhao-Jun, Han, Wei-Na, Zhang, Jun, Liu, Xiao-Jie, Tong, Jia-Qing, Qi, Jin-Shun
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2015
• Subjects: Amyloid beta-Peptides - toxicity; amyloid β-peptide (Aβ); Animals; Calcium - metabolism; Cells, Cultured; colivelin (CLN); Hippocampus - cytology; Homeostasis - drug effects; intracellular calcium overload; Intracellular Signaling Peptides and Proteins - therapeutic use; long term potentiation (LTP); Long-Term Potentiation - drug effects; Maze Learning - drug effects; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Morris water maze; Neuronal Plasticity - drug effects; Neurons - drug effects; Peptide Fragments - toxicity; Rats; Rats, Sprague-Dawley; amyloid β-peptide (Aβ); Morris water maze; intracellular calcium overload; colivelin (CLN); long term potentiation (LTP)
• ISSN: 1050-9631; 1098-1063
• DOI: 10.1002/hipo.22378

ABSTRACT Amyloid β peptide (Aβ) has been thought to be neurotoxic and responsible for the impairment of learning and memory in Alzheimer's disease (AD). Humanin (HN), a 24 amino acid polypeptide first identified from the unaffected occipital lobe of an AD patient, is believed to be neuroprotective against the AD‐related neurotoxicity. In this study, we investigated the neuroprotective effects of Colivelin (CLN), a novel HN derivative, against Aβ by using behavioral test, in vivo electrophysiological recording, and intracellular calcium imaging. Our results showed that intrahippocampal injection of CLN (0.2 nmol) effectively prevented Aβ25–35 (4 nmol)‐induced deficits in spatial learning and memory of rats in Morris water maze test; the suppression of in vivo hippocampal long term potentiation (LTP) by Aβ25–35 was nearly completely prevented by CLN; in addition, CLN pretreatment also effectively inhibited Aβ25–35–induced calcium overload in primary cultured hippocampal neurons. These results indicate that CLN has significant neuroprotective properties against Aβ, and CLN may holds great promise for the treatment and prevention of AD. © 2014 Wiley Periodicals, Inc.