Differential responses of amygdala and hippocampus consequent to A?40 and A?42 induced toxicity in the rat brain: A comparative study.

Amyloid beta (A?) peptides are the principal constituents of senile plaques of Alzheimer’s disease (AD) brain, and are thought to play an important role in the etiology and pathogenesis of AD. The present study assesses the responses of brain regions (hippocampus and amygdala) to amyloid toxicity in the light of behavioral and oxidative parameters. Aggregated A?¬¬40 and A?¬¬42 were stereotaxically injected into the hippocampus or amygdala, and their effects on cognitive (Morris water maze test) and non-cognitive (fear, anxiety, general emotional state: open field and light and dark chamber tests) behaviors were studied. Since human-specific social behaviors (empathy, sympathy etc.) also exist in rodents, the effect on these behaviors was also determined by three-chamber social behavior test. The oxidative stress generated by amyloid-? peptides is thought to contribute to the disease-associated behavioral deficits. Therefore, the present study also investigated the oxidative stress produced in the rat brain following amyloid injections. The oxidative stress produced by A? peptides was higher in the hippocampus compared with that in the amygdala. Similarly greater behavioral anomalies were caused in animals with intrahippocampal administration than in those with intraamygdalar administration. Thus, hippocampus showed a higher vulnerability to amyloid toxicity than amygdala. Furthermore, the results demonstrated that the oxidative stress spread from the injected site to distant brain regions like cortex, midbrain, cerebellum, and medulla. The results also showed that compared with A?40, A?42 generated higher levels of oxidative stress and produced more severe behavioral deficits.