title: The protective effect of melatonin on neural stem cell against LPS-induced inflammation.
abstract: Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs). Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO) production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases.
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Brain Korea 21 Project for Medical Science, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Juhyun
authors.identifier: 0000-0002-0727-8721
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Brain Korea 21 Project for Medical Science, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea ; BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: So Mang
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Department of Neurology, Seoul National University College of Medicine, Seoul 151-742, Republic of Korea.
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Brain Korea 21 Project for Medical Science, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea ; BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Jong Eun
authors.identifier: 0000-0001-6203-7413
authors.initials: JE
authors.lastname: Lee
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008550:Melatonin / Q000008:administration & dosage*; D058953:Neural Stem Cells / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D061251:Primary Cell Culture; D020011:Protective Agents / Q000008:administration & dosage*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; C490258:Nr2e1 protein, mouse; D020011:Protective Agents; D018160:Receptors, Cytoplasmic and Nuclear; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D009569:Nitric Oxide; D051497:Receptor, Fibroblast Growth Factor, Type 2; D008550:Melatonin