Spontaneous Running Wheel Improves Cognitive Functions of Mouse Associated with miRNA Expressional Alteration in Hippocampus Following Traumatic Brain Injury

Abstract

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.

miR21 is Associated with the Cognitive Improvement Following Voluntary Running Wheel Exercise in TBI Mice

“…1a). In agreement with the array data described before (Bao et al 2014), miR21 level significantly elevated in hippocampus of TBI-non-runners, compared with that of sham ones (p<0.05). This expressional increase of miR21 in hippocampal was reversed in TBI-runners (p<0.05) but did not reached the level of sham group.…”

“…In the present study, we investigated the effect of RW exercise on spatial learning and memory in relation to miR21 expression using a mouse model of TBI. Since we noted previously that miR21 is up-regulated in hippocampus by TBI (Bao et al 2014), we analyzed hippocampal expression of miR21 after TBI by in situ hybridization. Present evidences showed that mouse miR21 was expressed in the process, cytoplasm and nucleus of hippocampal neuron, and the elevated expression induced by TBI were reversed in the group treated with RW exercise.…”

“…This 3′ binding inhibits ribosome function, causing decapping of the capped 5′ end, deadenylation of the poly A tail, and degradation of the target mRNA (Filipowicz et al 2008). Previous study revealed that the up-regulation of miR21 in TBI mice were down-regulated by voluntary running wheel (RW) exercise (Bao et al 2014). We proposed that voluntary RW exercise induced the cognitive improvement of TBI mice, might be resulted from miR21 regulation in hippocampus.…”

“…These animals were then were individually housed in cages equipped with a RW each (n=7). The cages equipped with RW (diameter=12 cm, width=5 cm; Nalge Nunc International, Rochester, NY, USA) used for the voluntary exercise rotated freely and was attached to a receiver that monitored the number of revolutions (Vital Viewer Data Acquisition System software, Mini Mitter, Sunriver, OR, USA), as described before (Bao et al 2014). The mice were allowed to exercise ad libitum in individual cages with unlimited access to the running wheel.…”

Temporally-patterned deep brain stimulation in a mouse model of multiple traumatic brain injury

“…Attempts at amelioration have usually focused on environmental manipulations. Examples of these would include the traditional ‘enriched environment’ [5] and the opportunity for exercise on running wheels [6]. With rare exceptions (see Discussion), deep brain stimulation (DBS) has not been tried with the intention of improving behavioral arousal in the manner that is currently being attempted with human patients [7].…”