Beneficial effects of melatonin combined with exercise on endogenous neural stem/progenitor cells proliferation after spinal cord injury.
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.
Department of Rehabilitation Science, Graduate School of Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea. srlee@kribb.re.kr.
Youngjeon
Y
Lee
Department of Rehabilitation Science, Graduate School of Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea. charm-soo@hanmail.net.
Seunghoon
S
Lee
National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Chung-buk 363-883, Korea. srlee@kribb.re.kr.
Sang-Rae
SR
Lee
Department of Rehabilitation Science, Graduate School of Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea. charm-soo@hanmail.net.
Kanghui
K
Park
Department of Rehabilitation Science, Graduate School of Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea. charm-soo@hanmail.net.
Yunkyung
Y
Hong
Department of Rehabilitation Science, Graduate School of Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea. charm-soo@hanmail.net.
Minkyung
M
Lee
Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea. charm-soo@hanmail.net.
Sookyoung
S
Park
Department of Physical Therapy, College of Biomedical Science & Engineering, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea.
Yunho
Y
Jin
National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Chung-buk 363-883, Korea. srlee@kribb.re.kr.
Kyu-Tae
KT
Chang
Department of Rehabilitation Science, Graduate School of Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea. charm-soo@hanmail.net.
Yonggeun
Y
Hong
D000818:Animals; D049109:Cell Proliferation; D005081:Exercise Therapy; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000534:rehabilitation* / Q000628:therapy
D008550:Melatonin