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

作者：Lu Zhang, Yu Fang, Yajun Lian, Yuan Chen, Tianwen Wu, Yake Zheng, Huili Zong, Limin Sun, Ruifang Zhang, Zhenhua Wang, Yuming Xu · 发表于：PLoS ONE · 年份：2015 · DOI：10.1371/journal.pone.0122415 · 被引用次数：107 · 研究领域：Nerve injury and regeneration、Neurogenesis and neuroplasticity mechanisms、Neuroscience and Neuropharmacology Research

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.