Does the liver facilitate aging-related cognitive impairment: Conversation between liver and brain during exercise?

Liver, an important regulator of metabolic homeostasis, is critical for healthy brain function. In particular, age-related neurodegenerative diseases seriously reduce the quality of life for the elderly. As population aging progresses rapidly, unraveling the mechanisms that effectively delay aging has become critical. Appropriate exercise is reported to improve aging-related cognitive impairment. Whereas current studies focused on exploring the effect of exercise on the aging brain itself, ignoring the persistent effects of peripheral organs on the brain through the blood circulation. The aim of this paper is to summarize the communication and aging processes of the liver and brain and to emphasize the metabolic mechanisms of the liver-brain axis about exercise ameliorating aging-related neurodegenerative diseases. A comprehensive understanding of the potential mechanisms about exercise ameliorating aging is critical for improving adaptation to age-related brain changes and formulating effective interventions against age-related cognitive decline.

Effects of exercise-targeted hippocampal PDE-4 methylation on synaptic plasticity and spatial learning/memory impairments in D-galactose-induced aging rats.

Physical exercise reduces the effects of aging and cognitive decline by improving synaptic plasticity and spatial learning. However, the underlying neurobiological mechanisms are unclear. A total of 45 Male SPF Sprague-Dawley rats were acclimatized and then allocated into three groups, 15 in each group: the saline control (DC) group, D-gal-induced aging (DA) group, and D-gal-induced aging + exercise (DE) group. Six weeks of intraperitoneal injections of D-gal at a concentration of 100 mg/kg body weight/d was injected to establish model of aging in the DA and DE groups. Morris water maze test was implemented to evaluate the hippocampus related cognition. SOD activity and MDA was tested to assess the aging in all groups. H&E and Nissl staining was used to observe the histopathological changes of hippocampal neurons in aging rats. Quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining techniques were used to investigate the expression of synaptic genes and proteins in the hippocampus. Massarray methylation system was employed to measure the PDE-4 gene methylation level in rat hippocampal tissues. Our results demonstrated that exercise intervention improves cognitive function in D-gal-induced aging rats. The methylation of CpG sites in PDE-4 in the hippocampus was significantly increased. The physical exercise significantly increased PDE-4 gene methylation and effectively decreased PDE-4 gene and protein expression. These beneficial behavioral and morphological effects were attributed to PDE-4 methylation, which was activated cAMP/PKA/CREB pathway and improved synaptic plasticity. Exercise induced PDE-4 methylation is key mechanism underpinning the amelioration of learning/memory impairment, suggesting the potential efficacy of physical exercise training in delaying brain aging.

Visualization analysis of exercise intervention on Alzheimer disease based on bibliometrics: Trends, hotspots and topics.

BACKGROUND: As the challenges of an aging society continue to escalate, Alzheimer disease (AD) has emerged as a significant health, social, and public concern, garnering substantial attention. Exercise, as a safe, effective, and cost-efficient approach with the potential to mitigate brain aging, has garnered considerable interest. Nevertheless, there has been a limited research investigating the current trends, hotspots, and topics of exercise on AD. METHODS: The literature spanning from 2013 to 2022 was obtained from the Web of Science database, and CiteSpace VI was employed to conduct an analysis encompassing fundamental data, keywords, and co-citation analysis. RESULTS: A total of 9372 publications were included in the analysis. The annual number of publications has exhibited a gradual increase. The United States and China made significant contributions, with England showing higher citation rates and greater academic influence. The Journal of Alzheimers Disease, Neurosciences Neurology, Liu-Ambrose, Teresa represents the most published journal, discipline, and author, respectively. The research trends can be summarized as exploring functional changes and potential mechanisms related to exercise impact on AD. The hotspots in the research include the intersection of AD and diabetes mellitus, as well as the underlying effects induced by exercise. The topics of interest revolve around the application of emerging technologies in the context of exercise and AD. CONCLUSION: This bibliometric analysis has identified relevant trends, hotspots, and topics within the exercise intervention on AD. It offers a comprehensive overview that can equip researchers with valuable insights for future exploration and assist scholars in charting research trajectories in related domains.

Exercise preconditioning reduces ischemia reperfusion-induced focal cerebral infarct volume through up-regulating the expression of HIF-1α.

To study the effect and mechanism of exercise preconditioning on focal cerebral ischemia reperfusion induced cerebral infarction via rat model; Sixty Sprague Dawley rats were divided into three groups at random: ischemia reperfusion group (IR, n=24), sham group (sham, n=12) and exercise preconditioning group (EP, n=24). Group EP carried out moderate exercise preconditioning for 4 weeks (swimming with non-weight bearing, 60 minutes/day, 6 days/week), Rats in Group EP and IR were established cerebral ischemia reperfusion injury model by Zea Longa's thread method. The cerebral infarct volume in rat of different group was evaluated after 2%TTC staining, expression of HIF-1α in rats' brain was detected by real-time RT-PCR, immunohistochmeistry method and western blot. No cerebral infarction and significant expression of HIF-1α in Group sham. Compared with Group IR, there was smaller infarct volume and stronger HIF-1α expression in Group EP (P<0.05). Moderate exercise preconditioning reduces ischemia reperfusion induced focal cerebral infarct volume through up-regulating the expression of HIF-1α.

High intensity training induces alteration of the ubiquitin-proteasome system gene expression profile and structural changes in the ovaries.

The female reproductive system is highly sensitive to physiological stress. However, the mechanism(s) involved in dysfunction of the ovaries induced by high intensity exercise training remain unknown. In the present study, we established a rat model of high intensity exercise training, and investigated the morphological and functional changes in ovaries. Furthermore, we profiled the differential gene expression in the ovaries between high intensity exercise training rats and control rats by restriction fragment differential display PCR. Differentially expressed genes were validated by real-time PCR. The results showed that the weight and microstructure of the ovaries were significantly altered in the exercise training group rats. In addition, the levels of estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone were significantly decreased in the exercise training group rats compared with the control group rats. Immunohistochemistry revealed weak expression of estradiol, estrogen receptor and progesterone receptor in ovarian tissues from the high intensity exercise training group compared with the control group. Furthermore, the gene expression profiles of the exercise training and control group rats were analyzed, and differentially expressed genes, such as those involved in the ubiquitin-proteasome system, were identified. Our results indicate that high intensity exercise training can suppress the cellular function of the ovary glands. The mechanism may involve a series of alterations in the expression of genes particularly associated with the ubiquitin-proteasome system.