Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Efficacy of Lycium barbarum polysaccharide in adolescents with subthreshold depression: interim analysis of a randomized controlled study

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive disorder.In preclinical models of neurological and psychiatric diseases,Lycium barbarum polysaccharide(LBP)extracted from Goji berries had antidepressant effects including but not limited to anti-oxidative and anti-inflammatory properties.However,the effect of LBP on subthreshold depression is unclear.To investigate the clinical efficacy and safety of LBP for treating subthreshold depression in adolescents,we conducted a randomized,double-blind,placebo-controlled trial(RCT)with 29 adolescents with subthreshold depression recruited at The Fifth Affiliated Hospital of Guangzhou Medical University.The participants were randomly assigned to groups where they received either 300 mg LBP(LBP group,n=15,3 boys and 12 girls aged 15.13±2.17 years)or a placebo(placebo group,n=14,2 boys and 12 girls aged 15±1.71 years)for 6 successive weeks.Interim analyses revealed that the LBP group exhibited a greater change in Hamilton Depression Scale(HAMD-24)scores relative to the baseline and a higher remission rate(HAMD-24 total score≤7)at 6 weeks compared with the placebo group.Scores on the Beck Depression Inventory-II(BDI-II),Pittsburgh Sleep Quality Index(PSQI),Kessler Psychological Distress Scale(Kessler),and Screen for Child Anxiety-Related Emotional Disorders(SCARED)were similar between the LBP and placebo groups.No side effects related to the intervention were reported in either group.These results indicate that LBP administration reduced depressive symptoms in adolescents with subthreshold depression.Furthermore,LBP was well tolerated with no treatment-limiting adverse events.Clinical trials involving a larger sample size are needed to further confirm the anti-depressive effects of LBP in adolescents with subthreshold depression.This study was approved by the Medical Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical University(Guangzhou,China;approval No.L2019-08)on April 4,2019 and was registered on ClinicalTrials.gov(identifier:NCT04032795)on July 25,2019.

Alerting effects of light in healthy individuals: a systematic review and meta-analysis

Light plays an essential role in psychobiological and psychophysiological processes,such as alertness.The alerting effect is influenced by light characteristics and the timing of interventions.This meta-analysis is the first to systematically review the effect of light intervention on alertness and to discuss the optimal protocol for light intervention.In this meta-analysis,registered at PROSPERO(Registration ID:CRD42020181485),we conducted a systematic search of the Web of Science,PubMed,and PsycINFO databases for studies published in English prior to August 2021.The outcomes included both subjective and objective alertness.Subgroup analyses considered a variety of factors,such as wavelength,correlated color temperature(CCT),light illuminance,and timing of interventions(daytime,night-time,or all day).Twenty-seven crossover studies and two parallel-group studies were included in this meta-analysis,with a total of 1210 healthy participants(636(52%)male,mean age 25.62 years).The results revealed that light intervention had a positive effect on both subjective alertness(standardized mean difference(SMD)=-0.28,95%confidence interval(CI):-0.49 to-0.06,P=0.01)and objective alertness in healthy subjects(SMD=-0.34,95%CI:-0.68 to-0.01,P=0.04).The subgroup analysis revealed that cold light was better than warm light in improving subjective alertness(SMD=-0.37,95%CI:-0.65 to-0.10,P=0.007,I2=26%)and objective alertness(SMD=-0.36,95%CI:-0.66 to-0.07,P=0.02,I2=0).Both daytime(SMD=-0.22,95%CI:-0.37 to-0.07,P=0.005,I2=74%)and night-time(SMD=-0.32,95%CI:-0.61 to-0.02,P=0.04,I2=0)light exposure improved subjective alertness.The results of this meta-analysis and systematic review indicate that light exposure is associated with significant improvement in subjective and objective alertness.In addition,light exposure with a higher CCT was more effective in improving alertness than light exposure with a lower CCT.Our results also suggest that both daytime and night-time light exposure can improve subjective alertness.

Treadmill Exercise Reshapes Cortical Astrocytic and Neuronal Activity to Improve Motor Learning Deficits Under Chronic Alcohol Exposure

Alcohol abuse induces various neurological disorders including motor learning deficits,possibly by affecting neuronal and astrocytic activity.Physical exercise is one effective approach to remediate synaptic loss and motor deficits as shown by our previous works.In this study,we unrevealed the role of exercise training in the recovery of cortical neuronal and astrocytic functions.Using a chronic alcohol injection mouse model,we found the hyperreactivity of astrocytes along with dendritic spine loss plus lower neuronal activity in the primary motor cortex.Persistent treadmill exercise training,on the other hand,improved neural spine formation and inhibited reactive astrocytes,alleviating motor learning deficits induced by alcohol exposure.These data collectively support the potency of endurance exercise in the rehabilitation of motor functions under alcohol abuse.

Commentary on:“Human neural stem cell-derived artificial organelles to improve oxidative phosphorylation”

Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).