[[Gly14]-humanin protects against Aβ₃₁₋₃₅-induced impairment of spatial learning and memory in rats]

Amyloid β protein (Aβ) is closely involved in the pathogenesis of Alzheimer's disease (AD), and one of the main strategies for AD treatment is antagonizing the neurotoxicity of Aβ or even clearing the Aβ deposited in the brain. The present study was aimed to observe the effects of intrahippocampal injection of Aβ₃₁₋₃₅ on the spatial learning and memory of rats by using Morris water maze technique, and explore the neuroprotective effects and possible mechanism of [Gly14]-humanin (HNG) against Aβ-induced deficits in learning behavior. The results showed that bilateral intrahippocampal injection of 2.0 nmol Aβ₃₁₋₃₅ significantly increased the mean traveled distance of rats in searching for the hidden underwater platform and decreased the distance percentage in the target quadrant in probe test after withdrawal of platform, whereas pretreatment with HNG (0.2 nmol and 2.0 nmol) suppressed Aβ₃₁₋₃₅-induced increase in the traveled distance and decrease in swimming distance percentage. Application of Genistein (40 nmol), a specific tyrosine kinase inhibitor, almost completely blocked the antagonistic effects of HNG against Aβ₃₁₋₃₅. These results indicate that HNG can dose-dependently prevent against Aβ₃₁₋₃₅-induced impairment in spatial learning and memory of rats, and the neuroprotective effects of HNG might involve the activation of endogenous tyrosine kinase pathway, suggesting that up-regulation of the tyrosine kinase signaling by using HNG might be of great significance for the improvement of cognitive function in AD.