Effect of chronic forced swimming stress on whole brain radiation induced cognitive dysfunction and related mechanism

Abstract

Objective To explore whether chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction and possible mechanism. Methods Thirty-nine one month old male Sprague-Dawley rats were randomized into sham control group （ C ） , swimming group （ C-S ） , radiation group（ R） , and radiation plus swimming group（ R-S） . Radiation groups were given a single dose of 20 Gy on whole-brain. Rats in the swimming groups were trained with swimming of 15 min/d, 5 d/w. Rat behavior was performed 3 months after radiation in an order of free activity in an open field and the Morris water maze test including the place navigation and spatial probe tests. Then, the protein expressions of BDNF, P-ERK, T-ERK, P-CREB and T-CREB in the rat hippocampus tissue were assayed by Western blot. Results On the day 2, in the place navigation test of Morris water maze, the latency of swimming group was significantly shorter than that of sham group, the latency of sham group was significantly shorter than that of radiation group, and the latency of radiation swimming group was significantly shorter than that of radiation group（P〈0？05）. In the open field test, the latencies of the place navigation and spatial probe tests of Morris water maze had no significant difference among four groups （P〉0？05）. Western blot assay showed that the expressions of BDNF and its downstream signals including P-ERK and P-CREB were markedly reduced by radiation （ P 〈 0？05 ） , but this reduction was attenuated by the chronic forced swimming stress. Conclusion The chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction by up-regulating the expressions of BDNF and its downstream signal molecules of P-ERK and P-CREB in hippocampus. Key words: Whole-brain radiation; Cognitive dysfunction; Forced swimming stress; BDNF