Treadmill and wheel exercise alleviate lipopolysaccharide-induced short-term memory impairment by enhancing neuronal maturation in rats.

Lipopolysaccharide (LPS) is an endotoxin derived from Gram­negative bacteria, which induces brain inflammation. LPS­induced brain inflammation deteriorates hippocampus­dependent cognitive deficits. In the present study, we investigated the effects of forced treadmill exercise and voluntary wheel exercise on short­term memory in relation to neuronal maturation in LPS­induced brain inflammation of rats. Brain inflammation in rats was induced by an injection of LPS into the cerebral ventricle. Short­term memory was evaluated using a step­down avoidance task. Cell proliferation in the hippocampal dentate gyrus was determined by 5­bromo­2'­deoxyuridine (BrdU), a marker of new cells, immunohistochemistry. Western blot analysis for the determination of doublecortin (DCX), a marker of immature neurons and neuronal nuclear antigen (NeuN), a marker of mature neurons, was performed. In the present study, LPS­induced brain inflammation impaired short­term memory by increasing DCX expression and suppressing NeuN expression. These results suggest that LPS­induced brain inflammation disturbs neuronal maturation. The number of BrdU­positive cells in the hippocampal dentate gyrus was increased by LPS injection. This increase in the number of BrdU­positive cells can be ascribed to the increase in the number of of immature neurons following LPS injection. On the other hand, forced treadmill exercise and voluntary wheel exercise improved brain inflammation­induced short­term memory impairment by suppressing DCX expression and increasing NeuN expression, enhancing neuronal maturation. Forced treadmill exercise and voluntary wheel exercise showed similar efficacy. From these results, it can be inferred that forced treadmill exercise and voluntary wheel exercise may improve memory function deteriorated by brain inflammation.

Treadmill exercise ameliorates impairment of spatial learning ability through enhancing dopamine expression in hypoxic ischemia brain injury in neonatal rats.

Substantia nigra and striatum are vulnerable to hypoxic ischemia brain injury. Physical exercise promotes cell survival and functional recovery after brain injury. However, the effects of treadmill exercise on nigro-striatal dopaminergic neuronal loss induced by hypoxic ischemia brain injury in neonatal stage are largely unknown. We determined the effects of treadmill exercise on survival of dopamine neurons in the substantia nigra and dopaminergic fibers in the striatum after hypoxic ischemia brain injury. On postnatal 7 day, left common carotid artery of the neonatal rats ligated for two hours and the neonatal rats were exposed to hypoxia conditions for one hour. The rat pups in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 12 weeks, starting 22 days after induction of hypoxic ischemia brain injury. Spatial learning ability in rat pups was determined by Morris water maze test after last treadmill exercise. The viability of dopamine neurons in the substantia nigra and dopamine fibers in the striatum were analyzed using immunohistochemistry. In this study, hypoxic ischemia injury caused loss of dopamine neurons in the substantia nigra and dopaminergic fibers in the striatum. Induction of hypoxic ischemia deteriorated spatial learning ability. Treadmill exercise ameliorated nigro-striatal dopaminergic neuronal loss, resulting in the improvement of spatial learning ability. The present study suggests the possibility that treadmill exercise in early adolescent period may provide a useful strategy for the recovery after neonatal hypoxic ischemia brain injury.

Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice.

AIMS: Parkinson's disease is a debilitating neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons. We investigated the effects of treadmill exercise on dopaminergic neuronal loss and microglial activation using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P)-induced Parkinson's disease mice. MAIN METHODS: Parkinson's disease was induced in mice by injection of MPTP/P. The mice in the exercise groups were put on a treadmill to run for 30min/day, five times per week for four weeks. Motor balance and coordination was measured using rota-rod test. Expressions of inducible nitric oxide synthase (iNOS) and phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated NH(2)-terminal kinase (p-JNK), phosphorylated p-38 (p-p38), CD200, and CD200 receptor were determined by western blotting. Expressions of tyrosine hydroxylase (TH) and CD11b were evaluated by immunohistochemistry. KEY FINDINGS: Parkinson's disease mice displayed poor motor balance and coordination with loss of nigrostriatal dopaminergic neurons. iNOS expression was enhanced via up-regulation of phosphorylated mitogen-activated protein kinases (p-MAPKs) signaling, such as p-ERK, p-JNK, and p-p-38 in the Parkinson's disease mice. Microglial activation was also observed in the Parkinson's disease mice, showing increased CD11b expression with suppressed CD200 and CD200 receptor expressions. Treadmill exercise prevented the loss of nigrostriatal dopaminergic neurons, and ameliorated the motor balance and coordination dysfunction in the Parkinson's disease mice. Treadmill exercise suppressed iNOS expression via down-regulation of MAPKs and also inhibited microglial activation in the Parkinson's disease mice. SIGNIFICANCE: Treadmill exercise prevented dopaminergic neuronal loss by inhibiting brain inflammation through suppression of microglial activation in the Parkinson's disease mice.