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Chronic AdipoRon Treatment Mimics the Effects of Physical Exercise on Restoring Hippocampal Neuroplasticity in Diabetic Mice.

ABSTRACT: Administration of exercise mimetic drugs could be a novel therapeutic approach to combat comorbid neurodegeneration and metabolic syndromes. Adiponectin is an adipocyte-secreted hormone. In addition to its antidiabetic effect, adiponectin mediates the antidepressant effect of physical exercise associated with adult hippocampal neurogenesis. The antidiabetic effect of the adiponectin receptor agonist AdipoRon has been demonstrated, but its potential pro-cognitive and neurotrophic effects in the hippocampus under diabetic condition are still unclear. This study reported that chronic AdipoRon treatment for 2 weeks improved hippocampal-dependent spatial recognition memory in streptozotocin-induced diabetic mice. Besides, AdipoRon treatment increased progenitor cell proliferation and neuronal differentiation in the hippocampal dentate gyrus (DG) of diabetic mice. Furthermore, AdipoRon treatment significantly increased dendritic complexity, spine density, and N-methyl-D-aspartate receptor-dependent long-term potentiation (LTP) in the dentate region, and increased BDNF levels in the DG of diabetic mice. AdipoRon treatment activated AMPK/PGC-1α signalling in the DG, whereas increases in cell proliferation and LTP were not observed when PGC-1α signalling was pharmacologically inhibited. In sum, chronic AdipoRon treatment partially mimics the benefits of physical exercise for learning and memory and hippocampal neuroplasticity in the diabetic brain. The results suggested that AdipoRon could be a potential physical exercise mimetic to improve hippocampal plasticity and hence rescue learning and memory impairment typically associated with diabetes.

SUBMITTER: Lee TH

PROVIDER: S-EPMC8487422 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Physical inactivity and chronic pain are both major public health concerns worldwide. Although the health benefits of regular physical exercise are well-documented, few large epidemiological studies have investigated the association between specific domains of physical exercise and chronic pain in young adults. We sought to investigate the association between frequency, intensity and duration of physical exercise, and chronic pain. METHODS:Data stem from the SHoT2018-study, a national health survey for higher education in Norway, in which 36,625 fulltime students aged 18-35 years completed all relevant questionnaires. Chronic pain, defined according to the International Classification of Diseases 11th Revision (ICD-11), was assessed with a newly developed hierarchical digital instrument for reporting both distribution and characteristics of pain in predefined body regions. Physical exercise was assessed using three sets of questions, measuring the number of times exercising each week, and the average intensity and the number of hours each time. RESULTS:The majority (54%) of the students reported chronic pain in at least one location, and the prevalence was especially high among women. The overall pattern was an inverse dose-response association between exercise and chronic pain: the more frequent, harder or longer the physical exercise, the lower the risk of chronic pain. Similar findings were generally also observed for the number of pain locations: frequent exercise was associated with fewer pain locations. Adjusting for demographical, lifestyle factors and depression had little effect on the magnitude of the associations. CONCLUSION:Given the many health benefits of regular exercise, there is much to be gained in facilitating college and university students to be more physically active, ideally, thru a joint responsibility between political and educational institutions. Due to the cross-sectional nature of the study, one should be careful to draw a firm conclusion about the direction of causality.

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Chronic AdipoRon Treatment Mimics the Effects of Physical Exercise on Restoring Hippocampal Neuroplasticity in Diabetic Mice.

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