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The aims of the present study were to investigate whether exercise can improve the depression-like behavior caused by estrogen deficiency. Given that decreased level of brain-derived neurotrophic factor (BDNF) in many brain areas including hippocampus and prefrontal cortex is associated with estrogen deficiency-induced depression-like behavior, we also determined whether exercise affects the levels of BDNF and its receptor in hippocampus and prefrontal cortex (PFC). It was found that ovariectomy (OVX) caused an increase in depression-like behavior in rats and a decrease in BDNF level in hippocampus but not in PFC. The expression of TrkB, a high affinity BDNF receptor in hippocampus and PFC was not affected by OVX. 17β-estradiol (E2) treatment ameliorated depression-like behavior and increased BDNF level in hippocampus in OVX rats. Serum E2 level inversely correlated to depression-like behavior and positively correlated to BDNF level in hippocampus. Exercise ameliorated depression-like behavior, increased serum E2 level and BDNF level in hippocampus in OVX rats. The increased E2 level did not correlate to BDNF level but correlated with some of the behaviors in the rats subjected to exercise. Our results suggested that E2 maintains BDNF in hippocampus, thereby ameliorating depression-like behavior. Exercise amelioration of depression-like behavior in OVX rats is partly due to increased serum E2 level.

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