Cognitive improvement of mice induced by exercise prior to traumatic brain injury is associated with cytochrome c oxidase.

Though the evidence demonstrated that voluntary exercise programs could be implemented to enhance recovery of cognitive function induced by traumatic brain injury (TBI), the exact mechanisms were still not known. We proposed that the cognitive improvement induced by exercise in TBI mice is associated with cytochrome c oxidase (COX). To demonstrate this hypothesis, adult mice were housed with or without access to a running wheel (RW) for three weeks followed by TBI operation. Acquisition of spatial learning and memory retention was assessed by using the Morris Water Maze (MWM) on days 15 post TBI. The synaptic density was measured by Golji staining. Immunohistochemistry (IHC) for NeuN, GFAP and growth associated protein 43 (GAP43) were also performed. Using Western blot, the expressions of COX I, II, III, BDNF, synapsin I, synaptophysin (SYP) and GAP43 in hippocampus of TBI mice were determinated. Lastly, CcO activity and ATP amount were also detected. Results showed that voluntary exercise prior TBI: (i) counteracted the cognitive deficits and neuron and synaptic density loss associated with the injury; (ii) increased the levels of COX I, II, III, BDNF, synapsin I, SYP and GAP43; (iii) switched the mitochondrial CcO activity and ATP amounts. These studies demonstrated that the COX plays an important role in exercise's cognitive effects in TBI model and also provide evidence that RW training is a promise exercise for traumatically injured mice.