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Open AccessArticle

Elevated Serum Melatonin under Constant Darkness Enhances Neural Repair in Spinal Cord Injury through Regulation of Circadian Clock Proteins Expression

by Yunkyung Hong 1,2,3,4,†, Yunho Jin 2,3,4,†, Kanghui Park 3,5, Jeonghyun Choi 2,3,4, Hyunbon Kang 3,4,6, Sang-Rae Lee 7 and Yonggeun Hong 1,2,3,4,6,*
1
Department of Physical Therapy, College of Healthcare Medical Science & Engineering, Inje University, Gimhae 50834, Korea
2
Department of Rehabilitation Science, Graduate School of Inje University, Gimhae 50834, Korea
3
Ubiquitous Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gimhae 50834, Korea
4
Biohealth Products Research Center (BPRC), Inje University, Gimhae 50834, Korea
5
Department of Physical Therapy, Dong-Ju College, Busan 49318, Korea
6
Department of Physical Therapy, Graduate School of Inje University, Gimhae 50834, Korea
7
National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang 28116, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(2), 135; https://doi.org/10.3390/jcm8020135
Received: 12 December 2018 / Revised: 18 January 2019 / Accepted: 20 January 2019 / Published: 23 January 2019
We investigated the effects of environmental lighting conditions regulating endogenous melatonin production on neural repair, following experimental spinal cord injury (SCI). Rats were divided into three groups randomly: the SCI + L/D (12/12-h light/dark), SCI + LL (24-h constant light), and SCI + DD (24-h constant dark) groups. Controlled light/dark cycle was pre-applied 2 weeks before induction of spinal cord injury. There was a significant increase in motor recovery as well as body weight from postoperative day (POD) 7 under constant darkness. However, spontaneous elevation of endogenous melatonin in cerebrospinal fluid was seen at POD 3 in all of the SCI rats, which was enhanced in SCI + DD group. Augmented melatonin concentration under constant dark condition resulted in facilitation of neuronal differentiation as well as inhibition of primary cell death. In the rostrocaudal region, elevated endogenous melatonin concentration promoted neural remodeling in acute phase including oligodendrogenesis, excitatory synaptic formation, and axonal outgrowth. The changes were mediated via NAS-TrkB-AKT/ERK signal transduction co-regulated by the circadian clock mechanism, leading to rapid motor recovery. In contrast, exposure to constant light exacerbated the inflammatory responses and neuroglial loss. These results suggest that light/dark control in the acute phase might be a considerable environmental factor for a favorable prognosis after SCI. View Full-Text
Keywords: environmental lighting condition; endogenous melatonin; spinal cord injury; circadian clock; neural remodeling environmental lighting condition; endogenous melatonin; spinal cord injury; circadian clock; neural remodeling
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Hong, Y.; Jin, Y.; Park, K.; Choi, J.; Kang, H.; Lee, S.-R.; Hong, Y. Elevated Serum Melatonin under Constant Darkness Enhances Neural Repair in Spinal Cord Injury through Regulation of Circadian Clock Proteins Expression. J. Clin. Med. 2019, 8, 135.

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