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: Lu Zhang, Yu Fang, Yajun Lian, Yuan Chen, Tianwen Wu, Yake Zheng, Huili Zong, Limin Sun, Ruifang Zhang, Zhenhua Wang, Yuming Xu
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0122415 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25849905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Brain-Derived Neurotrophic Factor
• Peptide Fragments
• amyloid beta-protein (1-42)
• BDNF protein, human
• Extracellular Signal-Regulated MAP Kinases

Topics

• Alzheimer Disease (chemically induced, drug therapy, enzymology, physiopathology)
• Amyloid beta-Peptides (toxicity)
• Animals
• Brain-Derived Neurotrophic Factor (administration & dosage, metabolism, pharmacology, therapeutic use)
• Cognition (drug effects)
• Disease Models, Animal
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Hippocampus (drug effects, metabolism, physiopathology)
• Humans
• Injections
• Learning (drug effects)
• Male
• Memory (drug effects)
• Peptide Fragments (toxicity)
• Rats
• Rats, Sprague-Dawley
• Spatial Learning (drug effects)
• Up-Regulation (drug effects)