Spontaneous running wheel improves neuroprotection efficacy of ischemic postconditioning in mice following ischemia/reperfusion injury

Ischemic postconditioning(IP)has been shown to provide protection for ischemia/reperfusion(IR)injury,but its efficacy is limited.In this study we hypothesized that spontaneous running wheel(RW)could improve neuroprotection efficacy of IP for IR.We established mouse models of IR and showed that compared to Sham group,IR group had obvious brain infract and neurological dysfunction.In IR+IP group,brain infract and neurological dysfunction improved compared to IR group.However,in IR+IP+RW group brain infract and neurological dysfunction improved much better.TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR.However,the number of apoptotic cells was significantly reduced in RW+IP group.In addition,the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group,while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group.Moreover,in IR+IP+RW group,MDA level was further decreased and SOD level was further increased compared to IR+IP group.Finally,both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice.In conclusion,RW combined with IP reduces brain infract and neurological dysfunction in mice after IR,and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Voluntary wheel running ameliorated the deleterious effects of high-fat diet on glucose metabolism,gut microbiota and microbial-associated metabolites

Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.

A novel small-animal locomotor activity recording device for biological clock research

The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.

Rehabilitation following spinal cord injury:how animal models can help our understanding of exercise-induced neuroplasticity

Spinal cord injury is a devastating condition that is followed by long and often unsuccessful recovery after trauma. The state of the art approach to manage paralysis and concomitant impairments is rehabilitation, which is the only strategy that has proven to be effective and beneficial for the patients over the last decades. How rehabilitation influences the remodeling of spinal axonal connections in patients is important to understand, in order to better target these changes and define the optimal timing and onset of training. While clinically the answers to these questions remain difficult to obtain, rodent models of rehabilitation like bicycling, treadmill training, swimming, enriched environments or wheel running that mimic clinical rehabilitation can be helpful to reveal the axonal changes underlying motor recovery. This review will focus on the different animal models of spinal cord injury rehabilitation and the underlying changes in neuronal networks that are improved by exercise and rehabilitation.

Fat cell-secreted adiponectin mediates physical exercise-induced hippocampal neurogenesis: an alternative anti-depressive treatment?

Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.

Central monoaminergic systems are a site of convergence of signals conveying the experience of exercise to brain circuits involved in cognition and emotional behavior

Physical activity can enhance cognitive function and increase resistance against deleterious effects of stress on mental health. Enhanced cognitive function and stress resistance produced by exercise are conserved among vertebrates, suggesting that ubiquitous mechanisms may underlie beneficial ef- fects of exercise. In the current review, we summarize the beneficial effects of exercise on cognitive function and stress resistance and discuss central and peripheral signaling factors that may be critical for conferring the effects of physical activity to brain circuits involved in cognitive function and stress. Additionally, it is suggested that norepinephrine and serotonin, highly conserved monoamines that are sensitive to exercise and able to modulate behavior in multiple species, could represent a conver- gence between peripheral and central exercise signals that mediate the beneficial effects of exercise. Finally, we offer the novel hypothesis that thermoregulation during exercise could contribute to the emotional effects of exercise by activating a subset of temperature-sensitive serotonergic neurons in the dorsal raphe nucleus that convey anxiolytic and stress-protective signals to forebrain regions. Throughout the review, we discuss limitations to current approaches and offer strategies for future re- search in exercise neuroscience.

Selectively breeding for high voluntary physical activity in female mice does not bestow inherent characteristics that resemble eccentric remodeling of the heart,but the mini-muscle phenotype does

Physical activity engagement results in a variety of positive health outcomes,including a reduction in cardiovascular disease risk partially due to eccentric remodeling of the heart.The purpose of this investigation was to determine if four replicate lines of High Runner mice that have been selectively bred for voluntary exercise on wheels have a cardiac phenotype that resembles the outcome of eccentric remodeling.Adult females(average age 55 days)from the 4 High Runner and 4 non-selected control lines were anaesthetized via vaporized isoflurane,then echocardiographic images were collected and analyzed for structural and functional differences.High Runner mice in general had lower ejection fractions compared to control mice lines(2-tailed p=0.0236)and tended to have thicker walls of the anterior portion of the left ventricle(p=0.065).However,a subset of the High Runner individuals,termed mini-muscle mice,had greater ejection fraction(p=0.0006),fractional shortening percentage(p<0.0001),and ventricular mass at dissection(p<0.0027 with body mass as a covariate)compared to non-mini muscle mice.Mice from replicate lines bred for high voluntary exercise did not all have inherent positive cardiac functional or structural characteristics,although a genetically unique subset of mini-muscle individuals did have greater functional cardiac characteristics,which in conjunction with their previously described peripheral aerobic enhancements(e.g.,increased capillarity)would partially account for their increased VO2max.