Navishaa Govindasamy - School of Medicine, International Medical University, ۵۷۰۰۰ Kuala Lumpur, Malaysia
Kian Chung Chok - School of Health Science, International Medical University, ۵۷۰۰۰ Kuala Lumpur, Malaysia.
Pei Ying Ng - School of Postgraduate, International Medical University, ۵۷۰۰۰ Kuala Lumpur, Malaysia
Rhun Yian Koh - Division of Biomedical Science and Biotechnology, School of Health Science, International Medical University.
Soi Moi Chye - Division of Biomedical Science and Biotechnology, School of Health Science, International Medical University.

Background: Peripheral nerve injury (PNI) is a common condition that compromises motor and sensory functions. Peripheral nerves are known to have regenerative capability and the pineal hormone, melatonin, is known to aid nerve regeneration. However, the role of Schwann cells and the pathways involved remain unclear. Thus, the aim of this study is to identify the effects of melatonin on Schwann cell proliferation, dedifferentiation, and the involvement of nuclear factor kappa light chain enhancer of activated B cells (NFĸB), focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase, Src pathways in this process. Methods: Schwann cells was treated with melatonin and its proliferation and dedifferentiation were identified using MTT assay and immunofluorescence staining for SRY (sex determining region Y)-box ۲ (SOX۲). Next, the protein expressions of NF-ĸB, FAK and Src pathways were identified by Western blot. Results: MTT results confirmed increased proliferation of Schwann cells with melatonin treatment, and it was highest at ۱۰ μM melatonin. Immunofluorescent staining revealed an increase in the green fluorescence staining for SOX۲ in melatonin-treated cells, showing enhanced dedifferentiation. Western blot assay revealed melatonin increased phospho-NF-ĸB (PNF-ĸB), IKK-α, FAK (D۲R۲E), phospho-FAK (Tyr ۵۷۶/۵۷۷ and Tyr ۳۹۷) protein expressions as compared with control. However, Src (۳۲G۶), Lyn (C۱۳F۹), Fyn, Csk (C۷۴C۱) protein expressions were not increased as compared with control. Conclusions: Melatonin promotes Schwann cell proliferation and dedifferentiation via NF-ĸB, FAKdependent but Src-independent pathways.

Dedifferentiation, Melatonin, Peripheral nerve injury, Proliferation, Schwann cells. Introduction Peripheral