Background: Exercise can effectively attenuate withdrawal symptoms and reduce relapse, but it is unknown whether exercise of different intensities produces different results. This study aimed to systematically review the effects of different exercise intensities on withdrawal symptoms among people with substance use disorder (SUD).Methods: Systematic searches for randomized controlled trials (RCTs) on exercise, SUD, and abstinence symptoms were conducted via electronic databases, including PubMed, up to June 2022. Study quality was evaluated using the Cochrane Risk of Bias tool (RoB 2.0) for assessment of risk of bias in randomized trials. The meta-analysis was performed by calculating the standard mean difference (SMD) in outcomes of interventions involving light-, moderate-, and high-intensity exercise for each individual study using Review Manager version 5.3 (RevMan 5.3).Results: In total, 22 RCTs (n = 1,537) were included. Overall, exercise interventions had significant effects on withdrawal symptoms, but the effect size varied with exercise intensity and by outcome measure (i.e., for different negative emotions). Light-, moderate-, and high-intensity exercise reduced cravings after the intervention [SMD = −0.71, 95% CI = (−0.90, −0.52)], and there were no statistical differences between the subgroups (p > 0.05). Light-, moderate-, and high-intensity exercise reduced depression after the intervention [light, SMD = −0.33, 95% CI = (−0.57, −0.09); moderate, SMD = −0.64, 95% CI = (−0.85, −0.42); high, SMD = −0.25, 95% CI = (−0.44, −0.05)], with moderate-intensity exercise producing the best effect (p < 0.05). Only light- and moderate-intensity exercise relieved anxiety after the intervention [light, SMD = −0.48, 95% CI = (−0.71, −0.26); moderate, SMD = −0.58, 95% CI = (−0.85, −0.31)]. Only high-intensity exercise worked in alleviating stress [SMD = −1.13, 95% CI = (−2.22, −0.04)]. Both irritability and restlessness could be improved by light- and moderate-intensity exercise [irritability, SMD = −0.74, 95% CI = (−0.98, −0.50); restless, SMD = −0.72, 95% CI = (−0.98, −0.47)], and there were no statistical differences between the subgroups (p > 0.05). Moderate- and high-intensity exercise decreased withdrawal syndrome after the intervention [moderate, SMD = −0.30, 95% CI = (−0.55, −0.05); high, SMD = −1.33, 95% CI = (−1.90, −0.76)], with high-intensity exercise producing the best effects (p < 0.01).Conclusion: Overall, exercise leads to improvements in withdrawal symptoms in individuals with SUD, but these effects vary significantly between the exercise of different intensities and according to the type of withdrawal symptoms. Moderate-intensity exercise has the greatest benefits in improving depression and anxiety; high-intensity exercise has the greatest benefits in improving withdrawal syndrome.Systematic Review Registration:www.crd.york.ac.uk/PROSPERO/, identifier, CRD42022343791

Accumulating evidence underscores exercise as a straightforward and cost-effective lifestyle intervention capable of mitigating the risk and slowing the emergence and progression of Alzheimer’s disease (AD). However, the intricate cellular and molecular mechanisms mediating these exercise-induced benefits in AD remain elusive. The present study delved into the impact of treadmill exercise on memory retrieval performance, hippocampal synaptic plasticity, synaptic morphology, and the expression and activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors (AMPARs) in 6-month-old APP/PS1 mice. APP/PS1 mice (4-month-old males) were randomly assigned to either a treadmill exercise group or a sedentary group, with C57BL/6J mice (4-month-old males) as the control group (both exercise and sedentary). The exercise regimen spanned 8 weeks. Our findings revealed that 8-week treadmill exercise reversed memory retrieval impairment in step-down fear conditioning in 6-month-old APP/PS1 mice. Additionally, treadmill exercise enhanced basic synaptic strength, short-term potentiation (STP), and long-term potentiation (LTP) of the hippocampus in these mice. Moreover, treadmill exercise correlated with an augmentation in synapse numbers, refinement of synaptic structures, and heightened expression and activity of AMPARs. Our findings suggest that treadmill exercise improves behavioral performance and facilitates synaptic transmission by increasing structural synaptic plasticity and the activity of AMPARs in the hippocampus of 6-month-old APP/PS1 mice, which is involved in pre- and postsynaptic processes.

The excessive activation of microglia cell induced by adolescent intermittent ethanol (AIE) leads to neuroinflammation in the hippocampus. The endocannabinoid system plays a key role in the modulation of microglia activation. Accumulating evidence suggests that regular exercise improves learning and memory deficits in AIE models. The purpose of this study was to explore the effects of treadmill exercise intervention on the cognitive performance, activation of microglia cells and the expression of monoacylglycerol lipase (MAGL), cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R) in the hippocampus of AIE rats. Here, we show that AIE rats exhibited cognitive impairments, whereas the treadmill exercise improves the cognitive performance in AIE rats. In order to explore the possible mechanisms for the exercise-induced attenuation of cognitive disorder, we examined the neuroinflammation in the hippocampus. We found that treadmill exercise led to the decrease in the level of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and the increase in the level of anti-inflammatory cytokine (IL-10). In addition, we found that treadmill exercise reduced the excessive activation of the microglia cell in the hippocampus of AIE rats. Finally, we found that AIE led to a decrease in the expression of CB1R and CB2R in the hippocampus; however, the treadmill exercise further decreased the expression of CB2R in the hippocampus of AIE rats. Our results suggest that treadmill exercise attenuates AIE-induced neuroinflammation and the excessive activation of hippocampus microglial cells, which may contribute to the exercise-induced improvement of cognitive performance in AIE rats.

Background: One of the important mechanisms of depression is long-term high levels of inflammation. Exercise may help relieve depressive symptoms and is associated with anti-inflammatory effects. This research methodically assesses how various exercise modalities influence peripheral inflammatory markers in individuals with depression, so that more personalized and precise exercise schemes can be provided for people with depression to improve inflammation. Methods: Randomized controlled trials on depressive disorder, exercise, and inflammation published until May 2025 were screened in five databases. The Cochrane Risk of Bias tool (RoB2.0) was used to evaluate potential biases, with random effects meta-analyses gauging the impact of varying exercise regimens on peripheral inflammatory markers (CRP, IL-6 and TNF-α) involving exercise types, intensity, frequency, and length. Meta-regression analyses were employed to show the sources of heterogeneity and investigate potential moderator variables influencing CRP, IL-6, and TNF-α (PROSPERO CRD42024590612). Results: A total of 13 unique studies with 1004 participants were included. Overall, exercise training could alleviate depressive symptoms (SMD = −0.59, 95%CI: [−0.86, −0.32], I² = 61.7%, p < 0.001), and subgroup analysis showed that exercise lasting 8–12 weeks could reduce the level of TNF-α (MD = −0.74, 95%CI: [−1.30, −0.17], I² = 0, p < 0.05). Apparent discrepancies between subgroup and meta-regression findings were resolved by advanced modeling, which identified a significant non-linear relationship for TNF-α (quadratic term p = 0.003), characterized by a reduction peak at 8–12 weeks followed by a gradual increase, rather than a positive linear trend. Conclusions: Exercise could alleviate depressive symptoms in individuals with depression. However, the influence of exercise length on TNF-α levels has conflicting conclusions because of inconsistent evidence and substantial heterogeneity. Future high-quality trials with standardized biomarker measurements and better control of confounding factors are essential to determine whether the antidepressant effects of exercise are mediated by inflammation.

Purpose: Depression patients frequently report sleep disorder. Aerobic exercise is believed to improve sleep quality, but its effect on the overall sleep of depressed patients remains uncertain. This study systematically evaluates the effects of aerobic exercises at different intensities on subjective and objective sleep quality in participants diagnosed with depression or at high risk of depression, from studies covering various depression subtypes (including but not limited to geriatric depression, prenatal depression, and poststroke depression), and examines changes in depression, anxiety, and quality of life following aerobic exercise. Methods: Systematic searches for randomized controlled trials on aerobic exercise, depression, and sleep quality were conducted using PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2024. Meta-analysis was performed using Review Manager 5.4.1 and stata 17.0. Results: In total, 13 trials (n = 994) were included. Aerobic exercise significantly improved subjective sleep quality [SMD = − 0.52, 95% CI = (− 0.66, − 0.38)] but had no significant effect on objectively measured sleep efficiency [SMD = − 0.14, 95% CI = (− 0.46, 0.75)], total sleep time [SMD = 0.30, 95% CI = (− 0.03, 0.62)], or sleep latency [SMD = − 0.11, 95% CI = (− 0.76, 0.54)]. Additionally, aerobic exercise significantly alleviated depression [SMD = − 0.70, 95% CI = (− 0.93, − 0.47)] and anxiety [SMD = − 0.47, 95% CI = (− 0.74, − 0.19)], and enhanced quality of life [SMD = 0.64, 95% CI = (0.36, 0.92)]. Subgroup analyses revealed no significant differences among the different intensities. Conclusion: Aerobic exercise significantly improves subjective sleep quality, alleviates depressive and anxiety symptoms, and enhances quality of life in depression patients. Light-, moderate-, and vigorous-intensities aerobic exercises have equal positive effects on these indicators. Given the bidirectional relationship between sleep disturbances and depression progression, this study highlights the potential of exercise therapy to disrupt the vicious cycle. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/, identifier, CRD42023455212.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid‑β deposition, tau pathology, synaptic dysfunction, neuronal loss and neuroinflammation. Regular physical activity is a key non‑pharmacological strategy that can ameliorate cognitive impairment and multiple AD‑related pathological features across experimental models by improving mitochondrial function and quality control, strengthening antioxidant defenses, suppressing neuroinflammation and supporting synaptic plasticity. These effects are closely linked to enhanced neurotrophic signaling and cerebrovascular regulation, both of which contribute to resilience against AD‑associated cognitive decline. Fluoxetine, a selective serotonin reuptake inhibitor widely prescribed for depression, has also shown potential benefits in AD models, including modulation of mitochondrial and redox homeostasis, inflammatory signaling and neuroplasticity. The present review integrates evidence on the convergent and divergent molecular targets of exercise and fluoxetine within core AD pathways, highlighting scenarios in which combined interventions may produce synergistic effects, as well as conditions that could lead to antagonistic effects. By mapping shared nodes and potential points of interference, the present review aims to clarify mechanistic hypotheses and inform the design of optimized, clinically translatable strategies that integrate lifestyle and pharmacological approaches for AD.