Abstract
Alzheimer's disease (AD) is characterized by the presence of senile plaques and neurofibrillary tangles in the brain. The beta‐amyloid peptide (Aβ) is the primary constituent of the senile plaques, and has been proposed to be a key contributor to the neurodegeneration observed in AD. The molecular mechanisms underlying dendritic spine damage that is induced by Aβ toxicity in AD patients remain largely unknown. It has been suggested previously that the SNK‐SPAR signaling pathway is involved in activity‐dependent remodeling of synapses. The relationship between the SNK‐SPAR pathway and Aβ‐induced excitotoxicity, however, is poorly understood. The present study investigated the effects of bilateral intrahippocampal injection of Aβ peptide 1–40 (Aβ~1–40~) on learning and memory in the rat, and explored the mechanisms underlying the effects of this injection. We reported that bilateral injection of Aβ~1–40~ in rats resulted in impaired performance in the step‐down passive avoidance and Morris water maze tasks. Then we examined mRNA and protein expression levels in the different brain regions one week after injection with Aβ~1–40~ and found that the SNK‐SPAR signaling pathway was possibly involved in dendritic spine damage in the different brain regions of Aβ‐treated rats. These results demonstrate that the SNK‐SPAR pathway may possibly play a crucial role in Aβ‐induced excitotoxic damage in the central nervous system by regulating synaptic stability. © 2010 IUBMB IUBMB Life, 62(3): 214–221, 2010