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.