Abstract
Moderate exercise and mild hypothermia have protective effects against brain injury and neurodegeneration. Running in a cold environment alters exercise-induced hyperthermia and outcomes; however, evaluations of post-exercise cold exposure related to exercise benefits for the brain are relatively rare. We investigated the effects of 4°C cold exposure after exercise on exercise-induced thermal responses and neuroprotection in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced Parkinsonian mouse model. Male C57BL/6J mice were pretreated with MPTP for five consecutive days and follow-up treadmill exercise for 4 weeks. After 1-h running at a 22°C temperature, the mice were exposed to a 4°C environment for 2 h. An MPTP injection induced a transient drop in body and brain temperatures, while mild brain hypothermia was found to last for 4 weeks after MPTP treatment. Preventing brain hypothermia by exercise or 4°C exposure was associated with an improvement in MPTP-induced striatal uncoupling protein 4 (UCP4) downregulation and nigrostriatal dopaminergic neurodegeneration. However, 4°C exposure after exercise abrogated the exercise-induced beneficial effects and thermal responses in MPTP-treated mice, including a low amplitude of exercise-induced brain hyperthermia and body temperature while at rest after exercise. Our findings elucidate that post-exercise thermoregulation and UCP4 expression are important in the neuroprotective effects of exercise against MPTP toxicity.
Highlights
Moderate exercise promotes mitochondrial functions and upregulates survival factors that protect neurons from brain insults, including the movement disorders associated with Parkinson’s disease (PD) (Bayod et al, 2011; Wu et al, 2011; Koo et al, 2017)
We found that each MPTP injection induced an obvious decrease in core body temperature within 60 min, which returned to the baseline at around 210 min, while only a transient, slight increase was found in the saline (MPTP vehicle)-treated mice due to the handling required for injection (Figure 1B)
We found that the body and brain temperatures had significantly declined after MPTP treatment as compared with those in the saline-treated group
Summary
Moderate exercise promotes mitochondrial functions and upregulates survival factors that protect neurons from brain insults, including the movement disorders associated with Parkinson’s disease (PD) (Bayod et al, 2011; Wu et al, 2011; Koo et al, 2017). Cold Exposure Blocks Exercise Neuroprotection upregulating the nuclear-factor-E2-related factor 2 (Nrf2)-related antioxidant system (Tsou et al, 2015). We found that moderate treadmill exercise induces mild oxidative stress that leads to the activation of the endogenous Nrf antioxidant system to provide a defense against the lethal oxidative insults induced by MPP+. UCP1 can be found in brown adipose tissue for thermogenesis, while UCP2, UCP4, and UCP5 are expressed in the brain and involved in the brain’s neuroprotective functions (Kwon et al, 2010; Wu et al, 2014; de Oliveira Bristot et al, 2019). The effect of exercise on brain UCP4 and UCP5 expression remains uncharacterized
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