Traumatic brain injury (TBI) is an insult to the brain that results in impairments of cognitive and physical functioning. Both of human research and animal studies demonstrate that spontaneous exercise can facilitate neuronal plasticity and improve cognitive function in normal or TBI rodent models. However, the possible mechanisms underlying are still not well known. We postulated that spontaneous running wheel (RW) altered microRNA (miRNA) expressions in hippocampus of mice following TBI, which might be associated with the improvement in cognitive functions. In the present study, acquisition of spatial learning and memory retention was assessed by using the Morris water maze (MWM) test on days 15 post RW exercise. Then, microarray analyses in miRNA files were employed, and the expressional changes of miRNAs in the hippocampus of mice were detected. The results showed that spontaneous RW exercise (i) recovered the hippocampus-related cognitive deficits induced by TBI, (ii) altered hippocampal expressions of miRNAs in both of sham and TBI mice, and (iii) miR-21 or miR-34a was associated with the recovery process. The present results indicated that an epigenetic mechanism might be involved in voluntary exercise-induced cognitive improvement of mice that suffered from TBI.
MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular
changes that occur after traumatic brain injury (TBI). However, the changes and
possible roles of miRNAs induced by voluntary exercise prior to TBI are still not
known. In this report, the microarray method was used to demonstrate alterations in
miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a
running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decreased
the mortality rate and improved the recovery of the righting reflex in TBI mice, and
ii) differentially changed the levels of several miRNAs, upregulating some and
downregulating others. Furthermore, we revealed global upregulation of miR-21,
miR-92a, and miR-874 and downregulation of miR-138, let-7c, and miR-124 expression
among the sham-non-runner, TBI-non-runner, and TBI-runner groups. Quantitative
reverse transcription polymerase chain reaction data (RT-qPCR) indicated good
consistency with the microarray results. Our microarray-based analysis of miRNA
expression in mice cerebral cortex after TBI revealed that some miRNAs such as
miR-21, miR-92a, miR-874, miR-138, let-7c, and miR-124 could be involved in the
prevention and protection afforded by voluntary exercise in a TBI model.
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