title: Prophylactic treatment with melatonin before recurrent neonatal seizures: Effects on long-term neurobehavioral changes and the underlying expression of metabolism-related genes in rat hippocampus and cerebral cortex.
abstract: Although it has been suggested that the protective effect of melatonin against seizure-induced neurotoxicity involves inhibition of neuronal lipid peroxidation, current data concerning the exact molecular mechanism are still limited. This study was undertaken to investigate the changes in neurobehavioral, cognitive and lipid metabolism-related gene expressions in both hippocampus and cerebral cortex of rats subjected to recurrent neonatal seizures, and the effects of melatonin treatment before seizure (55mg/kg, 1mg/ml). 6-day-old (P6) SD rats were randomly divided into four groups of control (CONT, the same below), melatonin treated control (Mel), recurrent neonatal seizure (RS) and melatonin and RS combination treatment (Mel+RS). Neurological behavioral parameters of brain damage (plane righting reflex, negative geotaxis reaction reflex, Cliff avoidance reflex, forelimb suspension reflex) were observed on P31. Morris water maze test was performed during P29-P35. Then the protein levels of ACAT1, Cathepsin-E and Ca(2+)/calmodulin-dependent protein kinase II (CAMK II) in hippocampus and cerebral cortex were detected by western blot method. As expected, RS group showed a significant delay or reduce of the four reflexes, as well as bad performance in the Morris water maze test. Flurothyl-induced neurobehavioral toxicology was blocked by pre-treatment with melatonin. In parallel with these behavioral changes, gene expression by western blot method demonstrated that rats pretreated with melatonin (Mel+RS) showed a significant down-regulated expression of ACAT-1, Cathepsin-E and up-regulated CAMK II in hippocampus and cerebral cortex when compared with RS group. Our findings provide support for ACAT-1/Cathepsin-E as well as CaMK II being potential targets for the treatment of neonatal seizure-induced brain damage by melatonin.
authors.affiliation: Neurology Laboratory, Institute of Pediatrics, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, China. Electronic address: nyr2000@yeah.net.
authors.forename: Hong
authors.initials: H
authors.lastname: Ni
authors.affiliation: Neurology Laboratory, Institute of Pediatrics, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Neurology Laboratory, Institute of Pediatrics, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Neurology Laboratory, Institute of Pediatrics, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Key Laboratory of Cerebral Microcirculation at the Universities of Shandong, Department of Neurology, Affiliated Hospital of Taishan Medical College, Taian, Shandong 271000, China.
authors.forename: Bao-liang
authors.initials: BL
authors.lastname: Sun
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D020059:Cathepsin E / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005481:Flurothyl / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology*; D008660:Metabolism / Q000187:drug effects* / Q000235:genetics*; D051381:Rats; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D005481:Flurothyl; C000599076:ACAT1 protein, rat; D000101:Acetyl-CoA C-Acetyltransferase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020059:Cathepsin E; D008550:Melatonin
keywords: ACAT-1; CaMK II; Cathepsin-E; Melatonin; Neonatal seizure; Neurobehavioral toxicity