Aerobic Exercise Alleviates Ischemia-Induced Memory Impairment by Enhancing Cell Proliferation and Suppressing Neuronal Apoptosis in Hippocampus

Abstract

PurposeNeurogenic lower urinary tract dysfunction (NLUTD) is a possible consequence of several neurological disorders. NLUTD may produce debilitating symptoms and serious complications, such as chronic renal failure, and recurrent urinary tract infections. Many animal studies of NLUTD symptoms have focused on animal models of cerebral ischemia. In the present study, we investigated the effects of treadmill exercise on memory function and its relation to cell proliferation and apoptosis in the hippocampus, following transient global ischemia in gerbils.MethodsTo induce transient global ischemia in gerbil, both common carotid arteries were occluded for 5 minutes. Gerbils in the exercise groups were forced to run on a treadmill exercise for 30 minutes once a day for 2 weeks. Step-down avoidance task and Y maze task were performed. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-staining, immunohistochemistry for 5-bromo-2'-deoxyridine, doublecortin, caspase-3, and Western blot for brain-derived neurotrophic factor (BDNF), Bax, Bcl-2, cytochrome c, caspase-3 were conducted.ResultsIschemia caused memory impairment with an increase of cell proliferation, BDNF expression, and apoptosis in the hippocampus. Treadmill exercise improved memory function with further increase of cell proliferation and BDNF expression and a decrease of apoptosis.ConclusionsThe animal model that we have developed and our assessment of the relation between exercise and brain function can be useful tools for future investigations of NLUTD symptoms associated with stroke, particularly ischemic stroke. The present study suggests that treadmill exercise promoted the recovery of brain function after cerebral ischemia.

Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax/Bcl-2 proteins ratio and prevention of caspase-3 activation

“…Furthermore, according to previous studies, physical exercise improves cognitive function via increased cellular oxygenation [22]. Seo et al [23] indicated that treadmill exercise has protective effects on the hippocampal dentate gyrus granular cells in ischemic gerbils. Nevertheless, the mechanism by which physical exercise induces protection particularly in the CA3 area of the hippocampus following cerebral ischemia remains unclear.…”

Treatment with Enriched Environment Reduces Neuronal Apoptosis in the Periinfarct Cortex after Cerebral Ischemia/Reperfusion Injury

“…The binding of Bcl-2 and Bax could prevent the pore formation on the outer membranes of mitochondria, reduce the release of cytochrome c , inhibit the formation of the apoptosome and thus inhibit activation of caspase family [36]. Previous studies have shown that both passive and pre-ischemic exercise suppressed the apoptosis and reduced neurons loss in the periinfarct area via upregulating expression of Bcl-2 and maintaining the balance ratio of Bax/Bcl-2 [37-39]. Except for Bcl-2 family, caspase-3 is one of the most important downstream executors in the mitochondrial apoptotic pathway, which is considered as an indicator of neuronal apoptosis [40].…”

Exercise and Environmental Enrichment as Enablers of Task-Specific Neuroplasticity and Stroke Recovery

“…Poststroke exercise and EE further augment these processes in various stroke models [36,[55][56][57]. Interestingly, Komitova et al [57] reported that while poststroke EE enhanced neurogenesis in the subventricular zone, unlimited access to exercise beginning 24 h poststroke attenuated this effect.…”