title: Dynamic pattern of gene expression of ZnT-4, caspase-3, LC3, and PRG-3 in rat cerebral cortex following flurothyl-induced recurrent neonatal seizures.
abstract: Zinc transporters, plasticity-related genes, and autophagic/apoptotic pathway both are associated with developmental seizure-induced brain excitotoxicity. Here, for the first time, we report the timing of expression pattern of zinc transporter 4 (ZnT-4), plasticity-related gene 3 (PRG-3), specific marker of autophagic vacuoles (LC3), and apoptotic marker caspase-3 in cerebral cortex following neonatal seizures. A seizure was induced by inhalant flurothyl daily in neonatal Sprague-Dawley rats from postnatal day 6 (P6). Rats were assigned into the recurrent-seizure group (RS, seizures induced in six consecutive days) and the control group. At 1.5 h, 3 h, 6 h, 12 h, 24 h, 48 h, 7 days, and 14 days after the last seizure, the mRNA level of the four genes in cerebral cortex was detected using RT-PCR method. At an early period 6 h or 12 h after the last seizures, both ZnT-4 and LC3 showed significantly up-regulated mRNA level while PRG-3 showed significantly down-regulated mRNA level at 12 h in cerebral cortex of RS group than those at the corresponding time point in control group. In the long-term time point of 7 days after the last seizure, the mRNA level of caspase-3 down-regulated; meanwhile, there was up-regulated mRNA level of LC-3 in RS group when compared to the control rats. This is the first report investigating the gene expression pattern of ZnT-4, PRG-3, LC-3, and caspase-3 in the developing brain. The results suggest that the disturbed expression pattern of the four genes might play a role in the pathophysiology of recurrent neonatal seizure-induced acute and long-term brain damage.
authors.affiliation: Neurology Laboratory, Soochow University Affiliated Children's Hospital, No. 303, Jingde Road, Suzhou, 215003, People's Republic of China. nyr2000@yeah.net
authors.forename: Hong
authors.initials: H
authors.lastname: Ni
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.forename: Zhuo-jun
authors.initials: ZJ
authors.lastname: Xiao
authors.forename: Lu-yang
authors.initials: LY
authors.lastname: Tao
authors.forename: Mei-fang
authors.initials: MF
authors.lastname: Jin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017931:DNA Primers; D005481:Flurothyl / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D053148:Caspase 3; D017931:DNA Primers; D005481:Flurothyl; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; D010744:Phosphoric Monoester Hydrolases; C526109:Anxa3 protein, rat; C491596:Slc30a4 protein, rat; C570689:Plppr1 protein, rat