Previous studies have shown that aerobic exercise is an effective way to improve symptoms of Parkinson’s disease (PD). The aim of this study [PROSPERO CRD42022340730] was to explore the effects of aerobic exercises on balance, gait, motor function, and quality of life in PD patients. Searches were performed in PubMed, Web of Science, and EBSCO electronic databases. The Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. From 1287 search records initially identified, 20 studies were considered eligible for systematic review and meta-analysis. There was a significant effect of aerobic exercise on improving timed up and go test [standardized mean difference (SMD), −0.41 (95% CI, −0.61 to −0.22), p < 0.00001], Berg Balance Scale [0.99 (95% CI, 0.76 to 1.23), p < 0.00001], stride/step length [0.32 (95% CI, 0.03 to 0.61), p = 0.03], gait velocity [0.49 (95% CI, 0.20 to 0.78), p = 0.0009], Unified Parkinson’s Disease Rating Scale Part-III [-0.40 (95% CI, −0.55 to −0.24), p < 0.00001], and 6-minute walking test [0.35 (95% CI, 0.13 to 0.56), p = 0.002] in people with PD, but not in step cadence [−0.08 (95% CI, −0.43 to 0.27), p = 0.65] and Parkinson’s Disease Questionnaire-39 [−0.113 (95% CI, −0.39 to 0.13), p = 0.32]. Aerobic exercise had beneficial effects in improving balance, gait (velocity and stride/step length), and motor function in PD patients. However, aerobic exercise had no significant associations with the step cadence and quality of life in PD patients.

Background: A growing body of studies have examined the effect of exercise in people with multiple sclerosis (MS), while findings of available studies were conflicting. This meta-analysis aimed to explore the effects of exercise on balance, walking ability, walking endurance, fatigue, and quality of life in people with MS.Methods: We searched PubMed, Web of Science, Scopus, and Cochrane databases, through March 1, 2024. Inclusion criteria were: (1) RCTs; (2) included an intervention and control group; (3) had people with MS as study subjects; (4) had balance, walking ability, walking endurance, fatigue, or quality of life as the outcome measures. Exclusion criteria were: (1) non-English publications; (2) animal model publications; (3) review articles; and (4) conference articles. A meta-analysis was conducted to calculate weighted mean difference (WMD) and 95% confidence interval (CI). Cochrane risk assessment tool and Physiotherapy Evidence Database (PEDro) scale were used to evaluate the methodological quality of the included studies.Results: Forty studies with a total of 56 exercise groups (n = 1,300) and 40 control groups (n = 827) were eligible for meta-analysis. Exercise significantly improved BBS (WMD, 3.77; 95% CI, 3.01 to 4.53, P < 0.00001), TUG (WMD, −1.33; 95% CI, −1.57 to −1.08, P < 0.00001), MSWS-12 (WMD, −2.57; 95% CI, −3.99 to −1.15, P = 0.0004), 6MWT (WMD, 25.56; 95% CI, 16.34 to 34.79, P < 0.00001), fatigue (WMD, −4.34; 95% CI, −5.83 to −2.84, P < 0.00001), and MSQOL-54 in people with MS (WMD, 11.80; 95% CI, 5.70 to 17.90, P = 0.0002) in people with MS. Subgroup analyses showed that aerobic exercise, resistance exercise, and multicomponent training were all effective in improving fatigue in people with MS, with resistance exercise being the most effective intervention type. In addition, a younger age was associated with a larger improvement in fatigue. Furthermore, aerobic exercise and multicomponent training were all effective in improving quality of life in people with MS, with aerobic exercise being the most effective intervention type.Conclusion: Exercise had beneficial effects in improving balance, walking ability, walking endurance, fatigue, and quality of life in people with MS. Resistance exercise and aerobic exercise are the most effective interventions for improving fatigue and quality of life in people with MS, respectively. The effect of exercise on improving fatigue was associated with the age of the participants, with the younger age of the participants, the greater the improvement in fatigue.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371056, identifier: CRD42022371056.

A growing body of research has examined the effect of aerobic exercise on cognitive function in people with Alzheimer’s Disease (AD), but the findings of the available studies were conflicting. The aim of this study was to explore the effect of aerobic exercise on cognitive function in AD patients. Searches were performed in PubMed, Web of Science, and EBSCO databases from the inception of indexing until 12 November 2021. Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. From 1942 search records initially identified, 15 randomized controlled trials (RCTs) were considered eligible for systematic review and meta-analysis. Included studies involved 503 participants in 16 exercise groups (mean age: 69.2–84 years) and 406 participants (mean age: 68.9–84 years) in 15 control groups. There was a significant effect of aerobic exercise on increasing mini-mental state examination (MMSE) score in AD patients [weighted mean difference (WMD), 1.50 (95% CI, 0.55 to 2.45), p = 0.002]. Subgroup analyses showed that interventions conducted 30 min per session [WMD, 2.52 (95% CI, 0.84 to 4.20), p = 0.003], less than 150 min per week [WMD, 2.10 (95% CI, 0.84 to 3.37), p = 0.001], and up to three times per week [WMD, 1.68 (95% CI, 0.46 to 2.89), p = 0.007] increased MMSE score significantly. In addition, a worse basal cognitive status was associated with greater improvement in MMSE score. Our analysis indicated that aerobic exercise, especially conducted 30 min per session, less than 150 min per week, and up to three times per week, contributed to improving cognitive function in AD patients. Additionally, a worse basal cognitive status contributed to more significant improvements in cognitive function.

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naïve mice, whereas VTA HCN2 overexpression largely prevented CMS-induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors.

Alzheimer’s disease (AD) is characterized by deficits in learning and memory. A pathological feature of AD is the alterations in the number and size of synapses, axon length, dendritic complexity, and dendritic spine numbers in the hippocampus and prefrontal cortex. Treadmill exercise can enhance synaptic plasticity in mouse or rat models of stroke, ischemia, and dementia. The aim of this study was to examine the effects of treadmill exercise on learning and memory, and structural synaptic plasticity in 3×Tg-AD mice, a mouse model of AD. Here, we show that 12 weeks treadmill exercise beginning in three-month-old mice improves spatial working memory in six-month-old 3×Tg-AD mice, while non-exercise six-month-old 3×Tg-AD mice exhibited impaired spatial working memory. To investigate potential mechanisms for the treadmill exercise-induced improvement of spatial learning and memory, we examined structural synaptic plasticity in the hippocampus and prefrontal cortex of six-month-old 3×Tg-AD mice that had undergone 12 weeks of treadmill exercise. We found that treadmill exercise led to increases in synapse numbers, synaptic structural parameters, the expression of synaptophysin (Syn, a presynaptic marker), the axon length, dendritic complexity, and the number of dendritic spines in 3×Tg-AD mice and restored these parameters to similar levels of non-Tg control mice without treadmill exercise. In addition, treadmill exercise also improved these parameters in non-Tg control mice. Strengthening structural synaptic plasticity may represent a potential mechanism by which treadmill exercise prevents decline in spatial learning and memory and synapse loss in 3×Tg-AD mice.

Background: Current research suggests that continuous aerobic exercise can be effective in improving vascular endothelial function, while the effect between different intensities and durations of exercise is unclear. The aim of this study was to explore the effect of different durations and intensities of aerobic exercise on vascular endothelial function in different populations.Methods: Searches were performed in PubMed, Web of Science, and EBSCO databases. We included studies that satisfied the following criteria: 1) randomized controlled trials (RCTs); 2) including both an intervention and control group; 3) using flow-mediated dilation (FMD) as the outcome measure; and 4) testing FMD on the brachial artery.Results: From 3,368 search records initially identified, 41 studies were eligible for meta-analysis. There was a significant effect of continuous aerobic exercise on improving flow-mediated dilation (FMD) [weighted mean difference (WMD), 2.55, (95% CI, 1.93–3.16), p &lt; 0.001]. Specifically, moderate-intensity [2.92 (2.02–3.825), p < 0.001] and vigorous-intensity exercise [2.58 (1.64–3.53), p < 0.001] significantly increased FMD. In addition, a longer duration [<12 weeks, 2.25 (1.54–2.95), p < 0.001; ≥12 weeks, 2.74 (1.95–3.54), p < 0.001], an older age [age <45, 2.09 (0.78–3.40), p = 0.002; 45 ≤ age <60, 2.25 (1.49–3.01), p < 0.001; age ≥60, 2.62 (1.31–3.94), p < 0.001], a larger basal body mass index (BMI) [20 < BMI < 25, 1.43 (0.98–1.88), p &lt; 0.001; 25 ≤ BMI < 30, 2.49 (1.07–3.90), p < 0.001; BMI ≥ 30, 3.05 (1.69–4.42), p &lt; 0.001], and a worse basal FMD [FMD < 4, 2.71 (0.92–4.49), p = 0.003; 4 ≤ FMD < 7, 2.63 (2.03–3.23), p < 0.001] were associated with larger improvements in FMD.Conclusion: Continuous aerobic exercise, especially moderate-intensity and vigorous-intensity aerobic exercise, contributed to improving FMD. The effect of continuous aerobic exercise on improving FMD was associated with duration and participant’s characteristics. Specifically, a longer duration, an older age, a larger basal BMI, and a worse basal FMD contributed to more significant improvements in FMD.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=341442], identifier [CRD42022341442].