The role of exercise in brain DNA damage

Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unrepaired damaged DNA,which leads to neuronal death.In this way,DNA damage has been implicated in the pathogenesis of neurological disorders,cancer,and aging.Lifestyle factors,such as physical exercise,are neuroprotective and increase brain function by improving cognition,learning,and memory,in addition to regulating the cellular redox milieu.Several mechanisms are associated with the effects of exercise in the brain,such as reduced production of oxidants,up-regulation of antioxidant capacity,and a consequent decrease in nuclear DNA damage.Furthermore,physical exercise is a potential strategy for further DNA damage repair.However,the neuroplasticity molecules that respond to different aspects of physical exercise remain unknown.In this review,we discuss the influence of exercise on DNA damage and adjacent mechanisms in the brain.We discuss the results of several studies that focus on the effects of physical exercise on brain DNA damage.

DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

AIM:To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS:Rats were treated with an intraperitoneal injection of MK-801 [0.08(low-dose) and 0.16(highdose) mg/kg] or NaC l(vehicle control). In a first series of experiment,the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments,the whole brain of each animal was rapidly removed at 40 min post-injection,and different regions were separated:amygdala,cerebral cortex,hippocampus,hypothalamus,midbrain and ventral striatum on ice followed by DNA microarray(4 × 44 K whole rat genome chip) analysis.RESULTS:Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency(30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number(up- and down- regulations) of gene expressions in the cerebral cortex(378),midbrain(376),hippocampus(375),ventral striatum(353),amygdala(301),and hypothalamus(201) under low-dose(0.08 mg/kg) of MK-801. Under high-dose(0.16 mg/kg),ventral striatum(811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region.CONCLUSION:Acute MK-801 treatment increases synchrony of baseline gamma oscillations,and causes very early changes in gene expressions in six individual rat brain regions,a first report.

Look into my eyes:What can eye-based measures tell us about the relationship between physical activity and cognitive performance?

Background:There is a growing interest to understand the neurobiological mechanisms that drive the positive associations of physical activity and fitness with measures of cognitive performance.To better understand those mechanisms,several studies have employed eye-based measures(e.g., eye movement measures such as saccades,pupillary measures such as pupil dilation,and vascular measures such as retinal vessel diameter)deemed to be proxies for specific neurobiological mechanisms.However,there is currently no systematic review providing a comprehensive overview of these studies in the field of exercise-cognition science.Thus,this review aimed to address that gap in the literature.Methods:To identify eligible studies,we searched 5 electronic databases on October 23,2022.Two researchers independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise(TESTEX scale,for interventional studies) and the critical appraisal tool from the Joanna Briggs Institute(for cross-sectional studies).Results:Our systematic review(n=35 studies) offers the following main findings:(a) there is insufficient evidence available to draw solid conclusions concerning gaze-fixation-based measures;(b) the evidence that pupillometric measures,which are a proxy for the noradrenergic system,can explain the positive effect of acute exercise and cardiorespiratory fitness on cognitive performance is mixed;(c) physical training-or fitness-related changes of the cerebrovascular system(operationalized via changes in retinal vasculature) are,in general,positively associated with cognitive performance improvements;(d) acute and chronic physical exercises show a positive effect based on an oculomotor-based measure function(operationalized via antisaccade tasks);and(e) the positive association between cardiorespiratory fitness and cognitive performance is partly mediated by the dopaminergic system(operationalized via spontaneous eye-blink rate).Conclusion:This systematic review offers confirmation that eye-based measures can provide valuable insigt into the neurobiological mechanisms that may drive positive associations between physical activity and fitness and measures of cognitive performance.However,due to the limited number of studies utilizing specific methods for obtaining eye-based measures(e.g.,pupillometry,retinal vessel analysis,spontaneous eye blink rate) or investigating a possible dose-response relationship,further research is necessary before more nuanced conclusions can be drawn.Given that eye-based measures are economical and non-invasive,we hope this review will foster the future application of eye-based measures in the field of exercise-cognition science.

Does ergogenic effect of caffeine supplementation depend on CYP1A2 genotypes? A systematic review with meta-analysis

Background:The ergogenic effects of caffeine intake on exercise performance are well-established,even if differences exist among individuals in response to caffeine intake.The genetic variation of a specific gene,human cytochrome P450 enzyme 1A2(CYP1A2)(rs762551),may be one reason for this difference.This systematic review and meta-analysis aimed to comprehensively evaluate the influence of CYP1A2 gene types on athletes’exercise performance after caffeine intake.Methods:A literature search through 4 databases(Web of Science,PubMed,Scopus,and China National Knowledge Infrastructure)was conducted until March 2023.The effect size was expressed as the weighted mean difference(WMD)by calculating fixed effects meta-analysis if heterogeneity was not significant(I^(2)≤50%and p≥0.1).Subgroup analyses were performed based on AA and AC/CC genotype of CYP1A2.Results:The final number of studies meeting the inclusion criteria was 12(n=666 participants).The overall analysis showed that the cycling time trial significantly improved after caffeine intake(WMD=-0.48,95%confidence interval(95%CI):-0.83 to-0.13,p=0.007).In subgroup analyses,acute caffeine intake improved cycling time trial only in individuals with the A allele(WMD=-0.90,95%CI:-1.48 to-0.33,p=0.002),but not the C allele(WMD=-0.08,95%CI:-0.32 to 0.17,p=0.53).Caffeine supplementation did not influence the Wingate(WMD=8.07,95%CI:-22.04 to 38.18,p=0.60)or countermovement jump test(CMJ)performance(WMD=1.17,95%CI:-0.02 to 2.36,p=0.05),and these outcomes were not influenced by CYP1A2 genotype.Conclusion:Participants with the CYP1A2 genotype with A allele improved their cycling time trials after caffeine supplementation.However,compared to placebo,acute caffeine supplementation failed to increase the Wingate or CMJ performance,regardless of CYP1A2 genotype.

Exercise Against Aging:Darwinian Natural Selection Among Fit and Unfit Cells Inside Human Body

Exercise inevitably induces damages and triggers a brief inflammation in challenged tissues of the human body.Nevertheless,regular exercise is associated with improved physical fitness and lower all-cause mortality among adults in a dose-dependent manner.The paradox between destructive nature of exercise and its anti-aging benefit can be best explained by decreasing aged cell population of the human body in a Darwinian natural selection fashion,resulting in tissue renewal.In this concept,the unfit-to-fit cell ratio of a multicellular system increases during growth(expansion of cell population and size)and decreases after exercise challenges.Inflammation serves as an innate mechanism to recognize cells in danger and triggers clearance mechanism to eliminate unhealthy cells followed by regeneration.A recent finding of decreased p16INK4a+senescent cells together with CD68+macrophage infiltration in human skeletal muscle after resistance exercise supports this concept.The senescent cells are mostly stem cells located in capillaries surrounding myofibers,functioning to replace short-lived endothelial cells.They can be found in young men aged 20-25 years.In this context,exercise controls weight gain(i.e.cell number and size)and decrease senescent cell proportion in capillaries of the human body,providing benefits in physical fitness and increasing life expectancy.