title: Brain-derived neurotrophic factor ameliorates learning deficits in a rat model of Alzheimer's disease induced by aβ1-42.
abstract: 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.
authors: Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, China; Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors: Lu
authors: L
authors: Zhang
authors: Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, China; Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou University Zhengzhou, Henan, China.
authors: Yu
authors: Y
authors: Fang
authors: Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors: Yajun
authors: Y
authors: Lian
authors: Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors: Yuan
authors: Y
authors: Chen
authors: Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors: Tianwen
authors: T
authors: Wu
authors: Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors: Yake
authors: Y
authors: Zheng
authors: Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou University Zhengzhou, Henan, China.
authors: Huili
authors: H
authors: Zong
authors: Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou University Zhengzhou, Henan, China.
authors: Limin
authors: L
authors: Sun
authors: Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou University Zhengzhou, Henan, China.
authors: Ruifang
authors: R
authors: Zhang
authors: Department of Intensive Care Unit, First Affiliated Hospital, Zhengzhou University Zhengzhou, Henan, China.
authors: Zhenhua
authors: Z
authors: Wang
authors: Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, China; Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors: Yuming
authors: Y
authors: Xu
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007267:Injections; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C579455:BDNF protein, human; D048049:Extracellular Signal-Regulated MAP Kinases