Brain-Derived Neurotrophic Factor Ameliorates Learning Deficits in a Rat Model of Alzheimer's Disease Induced by Aβ1-42

• DOI: 10.1371/journal.pone.0122415
• Publication Date: 2015-04-07T18:19:27Z
• Authors: Lu Zhang; Yu Fang; Yajun Lian; Yuan Chen; Tianwen Wu; Yake Zheng; Huili Zong; Limin Sun; Ruifang Zhang; Zhenhua Wang; Yuming Xu
• Keywords: Male; 0301 basic medicine; Science; Spatial Learning; Hippocampus; Injections; Rats, Sprague-Dawley; 03 medical and health sciences; Cognition; Alzheimer Disease; Memory; Animals; Humans; Learning; Extracellular Signal-Regulated MAP Kinases; Amyloid beta-Peptides; Brain-Derived Neurotrophic Factor; Q; R; Peptide Fragments; Rats; Up-Regulation; 3. Good health; Enzyme Activation; Disease Models, Animal; Medicine; Research Article

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.