Melatonin Promotes Brain-Derived Neurotrophic

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ANIMAL STUDY e-ISSN 1643-3750 © Med Sci Monit, 2017; 23: 5951-5959 DOI: 10.12659/MSM.907592

Melatonin Promotes Brain-Derived Neurotrophic Factor (BDNF) Expression and Anti-Apoptotic Effects in Neonatal Hemolytic Hyperbilirubinemia via a Phospholipase (PLC)Mediated Mechanism

Received: 2017.10.17 Accepted: 2017.10.24 Published: 2017.12.16

Authors’ Contribution: Study Design  A Data Collection  B Analysis  C Statistical Data Interpretation  D Manuscript Preparation  E Literature Search  F Funds Collection  G

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Yong Luo Mei Peng Hong Wei

1 Department of Pediatrics, Yongchuan Hospital of Chongqing Medical University, Chongqing, P.R. China 2 Department of Infectious Diseases, Yongchuan Hospital of Chongqing Medical University, Chongqing, P.R. China 3 Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, P.R. China

Hong Wei, e-mail: [email protected] Departmental sources

Melatonin therapy shows positive effects on neuroprotective factor brain-derived neurotrophic factor (BDNF) expression and neuronal apoptosis in neonatal hemolytic hyperbilirubinemia. We hypothesized that melatonin promotes BDNF expression and anti-apoptotic effects in neonatal hemolytic hyperbilirubinemia through a phospholipase (PLC)-mediated mechanism. A phenylhydrazine hydrochloride (PHZ)-induced neonatal hemolytic hyperbilirubinemia model was constructed in neonatal rats. Four experimental groups – a control group (n=30), a PHZ group (n=30), a PHZ + melatonin group (n=30), and a PHZ + melatonin+U73122 (a PLC inhibitor) group (n=30) – were constructed. Trunk blood was assayed for serum hemoglobin, hematocrit, total and direct bilirubin, BDNF, S100B, and tau protein levels. Brain tissue levels of neuronal apoptosis, BDNF expression, PLC activity, IP3 content, phospho- and total Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV) expression, and phospho- and total cAMP response element binding protein (CREB) expression were also assayed. PHZ-induced hemolytic hyperbilirubinemia was validated by significantly decreased serum hemoglobin and hematocrit as well as significantly increased total and direct serum bilirubin (p

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