Abstract: Endogenous neural stem/progenitor cells (eNSPCs) proliferate and differentiate into neurons and glial cells after spinal cord injury (SCI). We have previously shown that melatonin (MT) plus exercise (Ex) had a synergistic effect on functional recovery after SCI. Thus, we hypothesized that combined therapy including melatonin and exercise might exert a beneficial effect on eNSPCs after SCI. Melatonin was administered twice a day and exercise was performed on a treadmill for 15 min, six days per week for 3 weeks after SCI. Immunohistochemistry and RT-PCR analysis were used to determine cell population for late response, in conjunction with histological examination and motor function test. There was marked improvement in hindlimb function in SCI+MT+Ex group at day 14 and 21 after injury, as documented by the reduced size of the spinal lesion and a higher density of dendritic spines and axons; such functional improvements were associated with increased numbers of BrdU-positive cells. Furthermore, MAP2 was increased in the injured thoracic segment, while GFAP was increased in the cervical segment, along with elevated numbers of BrdU-positive nestin-expressing eNSPCs in the SCI+MT+Ex group. The dendritic spine density was augmented markedly in SCI+MT and SCI+MT+Ex groups.These results suggest a synergistic effect of SCI+MT+Ex might create a microenvironment to facilitate proliferation of eNSPCs to effectively replace injured cells and to improve regeneration in SCI.
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Lee, Y.; Lee, S.; Lee, S.-R.; Park, K.; Hong, Y.; Lee, M.; Park, S.; Jin, Y.; Chang, K.-T.; Hong, Y. Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury. Int. J. Mol. Sci. 2014, 15, 2207-2222.
Lee Y, Lee S, Lee S-R, Park K, Hong Y, Lee M, Park S, Jin Y, Chang K-T, Hong Y. Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury. International Journal of Molecular Sciences. 2014; 15(2):2207-2222.
Lee, Youngjeon; Lee, Seunghoon; Lee, Sang-Rae; Park, Kanghui; Hong, Yunkyung; Lee, Minkyung; Park, Sookyoung; Jin, Yunho; Chang, Kyu-Tae; Hong, Yonggeun. 2014. "Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury." Int. J. Mol. Sci. 15, no. 2: 2207-2222.