Journal Article

Brain-derived neurotrophic factor ameliorates learning deficits in a rat model of Alzheimer's disease induced by aβ1-42

Sun, Limin, Zhang, Ruifang, Xu, Yuming, Zhang, Lu, Fang, Yu, Chen, Yuan, Zheng, Yake, Lian, Yajun, Wu, Tianwen, Wang, Zhenhua, Zong, Huili

2015

Overview

An emerging body of data suggests that the early onset of Alzheimer's disease (AD) is associated with decreased brain-derived neurotrophic factor (BDNF). Because BDNF plays a critical role in the regulation of high-frequency synaptic transmission and long-term potentiation in the hippocampus, the up-regulation of BDNF may rescue cognitive impairments and learning deficits in AD. In the present study, we investigated the effects of hippocampal BDNF in a rat model of AD produced by a ventricle injection of amyloid-β1-42 (Aβ1-42). We found that a ventricle injection of Aβ1-42 caused learning deficits in rats subjected to the Morris water maze and decreased BDNF expression in the hippocampus. Chronic intra-hippocampal BDNF administration rescued learning deficits in the water maze, whereas infusions of NGF and NT-3 did not influence the behavioral performance of rats injected with Aβ1-42. Furthermore, the BDNF-related improvement in learning was ERK-dependent because the inhibition of ERK, but not JNK or p38, blocked the effects of BDNF on cognitive improvement in rats injected with Aβ1-42. Together, our data suggest that the up-regulation of BDNF in the hippocampus via activation of the ERK signaling pathway can ameliorate Aβ1-42-induced learning deficits, thus identifying a novel pathway through which BDNF protects against AD-related cognitive impairments. The results of this research may shed light on a feasible therapeutic approach to control the progression of AD.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alzheimer Disease - chemically induced / Alzheimer Disease - drug therapy / Alzheimer Disease - enzymology / Alzheimer Disease - physiopathology / Alzheimer's disease / Alzheimers disease / Amyloid beta-Peptides - toxicity / Animals / Brain / Brain-derived neurotrophic factor / Brain-Derived Neurotrophic Factor - administration & dosage / Brain-Derived Neurotrophic Factor - metabolism / Brain-Derived Neurotrophic Factor - pharmacology / Brain-Derived Neurotrophic Factor - therapeutic use / Cognition - drug effects / Dementia / Disease Models, Animal / Enzyme Activation - drug effects / Extracellular Signal-Regulated MAP Kinases - metabolism / Gene expression / Growth factors / Hippocampus / Hippocampus - drug effects / Hippocampus - metabolism / Hippocampus - physiopathology / Hospitals / Humans / Injection / Injections / Intensive care / JNK protein / Kinases / Laboratories / Learning - drug effects / Male / Maze learning / Memory / Memory - drug effects / Neurology / Neurons / Neurotrophic factors / Peptide Fragments - toxicity / Peptides / Proteins / Rats / Rats, Sprague-Dawley / Rodents / Spatial Learning - drug effects / Up-Regulation - drug effects