Abstract
Recent evidences revealed that the alteration of microRNAs (miRNAs) might be associated with neuroplasticity induced by voluntary running wheel (RW) exercise in mice suffered from traumatic brain injury (TBI). In the present study, we explored the possible role of miR21 involved in the cognitive improvement following voluntary RW in TBI mice. Firstly, in situ hybridization and quantitative real-time PCR (qRT-PCR) were employed to determine the hippocampal expression and location of miR21 in TBI mice with or without spontaneous RW. Either miR21-mimics/plenti-miR21 or miR21-agomir/miR21-sponge was employed to regulate the miR21 expression in vivo and in vitro. Acquisition of spatial learning and memory retention was assessed by Morris Water Maze (MWM) test. Golgi stain was also performed to evaluate the alteration of hippocampal dendrite. Our finding confirmed that the elevated miR21 level in hippocampal post-TBI was significantly reduced by spontaneous RW. Overexpression of miR21 in TBI mice with spontaneous RW induced deteriorations in spatial learning and memory retention by significant decreases in the somata size and branch points of the hippocampus neurons. In vitro transduction with miR21 also reduced the neurite extension and the area of cultured hippocampal neuron. However, miR21 down-regulation reversed these effects. The present data strongly suggest that miR21 is an important molecule that has been involved in neuroprotection induced by voluntary RW exercise post-TBI.
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Acknowledgments
We thank Dr. Kevin J. Wells for his valuable comments during the preparation of this manuscript. This work is supported by National Natural Science Foundation of China (Grant NO.81100911, http://isisn.nsfc.gov.cn/egrantweb/), the Special Fund of the Applied Basic Research Programs of Yunnan Province associated with Kunming Medical University in China (Grant NO.2013FB116, http://61.166.241.213/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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The authors declare that they have no competing interest.
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Tao Hu, Feng-Jie Zhou and Ye-Fei Chang contributed equally to this work.
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Hu, T., Zhou, FJ., Chang, YF. et al. miR21 is Associated with the Cognitive Improvement Following Voluntary Running Wheel Exercise in TBI Mice. J Mol Neurosci 57, 114–122 (2015). https://doi.org/10.1007/s12031-015-0584-8
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DOI: https://doi.org/10.1007/s12031-015-0584-8