Colivelin Ameliorates Amyloid β Peptide-Induced Impairments in Spatial Memory, Synaptic Plasticity, and Calcium Homeostasis in Rats

Amyloid peptide (A) 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 A 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 A25-35 (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 A25-35 was nearly completely prevented by CLN; in addition, CLN pretreatment also effectively inhibited A25-35-induced calcium overload in primary cultured hippocampal neurons. These results indicate that CLN has significant neuroprotective properties against A, and CLN may holds great promise for the treatment and prevention of AD. (c) 2014 Wiley Periodicals, Inc.