Treadmill exercise improves memory by up-regulating dopamine and down-regulating D(2) dopamine receptor in traumatic brain injury rats

Traumatic brain injury (TBI) causes a variety of neuropathological manifestations including cognitive, emotional, physiological and psychological deficits. Physical exercise is known to ameliorate neurological impairments induced by various brain injuries. We investigated the effects of treadmill exercise on memory impairments due to TBI in relation to dopamine and D(2) dopamine receptor. TBI was induced with an electromagnetic-controlled cortical impact device. The rats in the exercise groups were scheduled to run on a treadmill for 30 min once a day for 28 days after TBI induction. Then, step-down avoidance task, radial 8-arm maze test, immunohistochemistry for tyrosine hydroxylase (TH), and western blot for D(2) dopamine receptor were performed. TBI impaired short-term and spatial learning memories. TBI decreased TH expressions in the prefrontal cortex (PFC), striatum, hippocampus dentate gyrus, and substantia nigra (SN). By contrast, the expressions of D(2) dopamine receptor in the PFC, striatum, hippocampus, and SN were increased by TBI. Treadmill exercise alleviated the impairments of short-term and spatial learning memories observed in TBI rats. TH expression was decreased and D(2) dopamine receptor expression was increased in TBI rats. Treadmill exercise enhanced TH expression and suppressed D(2) dopamine receptor expression in TBI rats. TBI deteriorated short-term and spatial learning memories, in contrast, treadmill exercise alleviated the TBI-induced memory impairments by up-regulating dopamine level and down-regulating D(2) dopamine receptor expression.