The neuroprotective effects of N-stearoyl-L-tyrosine (NSTyr) on cognitive function and neuronal plasticity during chronic cerebral hypoperfusion (CCH) in rats were investigated. After induction of CCH, NSTyr was administered daily for 3 months intraperitoneally. Cognitive functions were evaluated by Morris water maze and hippocampal long-term potentiation (LTP). Neuropathological changes were examined using light micrograph and Fluoro-Jade B staining. Neuronal plasticity was assessed by measuring the expression of MAP-2, GAP-43 and synaptophysin on hippocampal regions of rats with immunohistochemistry and western blotting. CCH resulted in significant spatial memory impairment and inhibition of LTP, and led to neurodegeneration in the CA1 region of the hippocampus in the model rats compared with the sham-operated rats. In the model rats treated with NSTyr, cognitive function improved. The expression levels of MAP-2 and synaptophysin protein in hippocampal areas in the model rats were less than those in the sham-operated rats, and increased in the model rats treated with NSTyr. However, no statistical significance of GAP-43 expression among the sham, model and NSTyr groups was observed. These data indicate that NSTyr exerts protective effects on cognitive function of rats after CCH, which may be related to the changes of neurodegeneration and neuronal plasticity in the hippocampal area of rats.
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