Objective:To investigate possible neuromodulatory mechanisms involved in the involvement of parvalbu-min(PV)expression in the basal ganglia output nuclei,entopeduncular nucleus(EPN)and substantia nigra pars etic-ulata(SNr),in exercise-induced chronic fatigue impairs working memory capacity.Methods:Male SD rats were divid-ed into control group and Fatigue group by random number method,and a three-stage incremental load treadmill training program was selected to establish a chronic exhaustion exercise-induced fatigue rat model.The working memory ability of rats was assessed by the Y-maze autonomous alternation experiment.Immunohistochemical staining was used to ob-serve the expression of parvalbumin(PV)positive neurons and cysteine aspartate-specific protease-3(caspase-3)in EPN and SNr of rats.Results:The accuracy of voluntary alternation in the fatigue group was obviously lower than that in control group(P＜0.05).The results of immunohistochemical staining showed that the density of PV positive neu-rons and the degree of positive fiber staining in EPN and SNr in the fatigue group were obviously lower than those in the control group(P＜0.05,P＜0.01).The number of caspase-3 positive cells per unit area of EPN and SNr in the fa-tigue group was obviously higher than that in the control group(P＜0.05,P＜0.01).Conclusion:The mechanism of impairing working memory in rats caused by exercise-induced chronic fatigue may be related to the apoptosis of PV posi-tive neurons in EPN and SNr.

AIM:To explore the intensity-dependent effects of exercises to alleviate fear memory generaliza-tion in post-traumatic stress disorder(PTSD)and the underlying mechanism.METHODS:Male C57 BL/6J mice were randomly divided into the control group,PTSD group,high-intensity exercise(PTSD-High)group,and low-intensity exer-cise(PTSD-Low)group.PTSD model were created via using a combination of conditioned foot shock(CF)and single-pro-longed stress(SPS).The contextual fear test was used to test the mice's ability to discriminate safety situations from fear condition.Immunofluorescence observed and quantified the newborn immature neurons in the DG area of the mice's hippo-campus.ELISA was used to determine the secretion level of serum tissue adiponectin.RESULTS:(1)The immobility times for the PTSD-High and Control groups were significantly lower than those of the PTSD group.(2)Immunofluores-cence analysis showed that the cell density,dendritic branching points and length of newborn immature neurons were ele-vated in High and Low groups compared to the PTSD group.(3)Adiponectin levels in the serum of the control and PTSD-High group were significantly higher than those in the PTSD group and PTSD-Low group.CONCLUSION:Fear memory establishment in PTSD mice is associated with decreased hippocampal neurogenesis.High-intensity exercise ameliorated fear memory by enhancing adiponectin secretion and promoting hippocampal neurogenesis.High-intensity exercise exerted better improvement of brain functions to PTSD model.

Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.