Excessive Treadmill Training Enhances Brain-Specific MicroRNA-34a in the Mouse Hippocampus

Abstract

Background: An imbalance between total training load and total recovery may cause overtraining (OT). The purpose of the present study was to verify the effects of OT on the expression of brain-derived neurotrophic factor (BDNF), its receptor tropomyosin receptor kinase B (TrkB) and p75 and the dynamic expression patterns of brainspecific miR-34a and miR-124 or inflammation-related miR-21 and miR-132 in the mouse hippocampus.Method: Eight weeks old C57BL/6J mice were randomly assigned to the control (CON), normal training (NT) and OT groups. An 8-week OT training protocol was applied to evaluate the phenotype of mice endurance (incremental load test, ILT) and cognitive capacity (Morris water maze test). We used qRT-PCR and immunoblotting to detect changes in the molecular level of hippocampal samples.Result: Compared with the CON, both NT and OT decreased bodyweight after 8-week training. After 8-week of training, NT increased the exhaustion velocity (EV) while the EV of OT was lower than NT. Mice in NT decreased the escape latency than CON. The percentage of time spent in the probe quadrant and the number of crossing platform times in NT were higher than CON and OT. The BDNF, p75 and TrkB mRNA levels were increased in NT than CON, only the p75 mRNA was increased in OT. The NT exhibited increased protein levels of BDNF and TrkB compared to CON. The protein expression of BDNF was decreased in OT than NT and CON. The protein level of p75 in the OT was higher than in NT and CON. In addition, the phosphorylation level of TrkB in OT was higher than CON and NT. Only the miR-34a level was increased in the OT. Moreover, the expression of miR-34a was found to be negatively correlated with the expression of BDNF, and the increase in miR-34a level was accompanied by a decrease in performance.Frontiers in Molecular Neuroscience | www.frontiersin.org January 2020 | Volume 13 | Article 7 Xu et al. Brain-Specific MicroRNA-34a and Excessive TrainingConclusion: In summary, the training-evoked increase in the BDNF level may help to improve performance, whereas this conditioning is lost after OT. Moreover, miR-34a potentially mediated changes in the expression of BDNF and may reflect the decrease in performance after OT.

iMS‐Bmal1−/− mice show evident signs of sarcopenia that are counteracted by exercise and melatonin therapies

“…Exercise consisted of 2 weeks on a horizontal treadmill (5 days/week, 30 min/day, up to a speed of 30 cm/s) plus 2 days of recovery required for reducing animal stress, according to previous reports, 24 starting at 12 weeks of age.…”

Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer

“…Exercise increases the release of BDNF from the human brain [ 231 , 232 ] suggesting that exercise also mediates central BDNF production in humans. It has been suggested that miR-34a potentially can also mediate changes in BDNF expression and may reflect the decrease in performance after overtraining [ 233 ].…”

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“…Although Feter et al, 2019 reported that interventions lasting at least 12 weeks with a session duration of 40 min would be the most prominent strategy for increasing BDNF levels in healthy or unhealthy adults (Feter et al, 2019). In contrast, overtraining seems to reduce BDNF level, but upregulates its receptors of "p75" and tropomyosin receptor kinase B (TRKB), in intact mice (Xu et al, 2020). Therefore, BDNF releasing system keeps enough sensitivity to be elevated, whenever encountering the different forms of exercise training, although acute exercising is more prominent.…”