title: Acylated ghrelin protects hippocampal neurons in pilocarpine-induced seizures of immature rats by inhibiting cell apoptosis.
abstract: Ghrelin has two major molecular forms, acylated ghrelin (AG) and unacylated ghrelin (UAG). Only AG to bind growth hormone secretagogue receptor 1a (GHSR-1a) has central endocrine activities. An antiapoptotic effect of AG in cortical neuronal cells has recently been reported. However, whether there is a neuroprotective effect of AG in hippocampal neurons of pilocarpine-induced seizures in rats, is still unknown. Therefore, in the present study, the underlying mechanism of AG on lithium-pilocarpine-induced excitotoxicity was examined in the hippocampus of rat. The results showed that AG inhibited pilocarpine-induced apoptosis. Exposure of rats to the receptor-specific antagonist D-Lys-3-GHRH-6 abolished the protective effects of AG against epilepsy. Administration of AG resulted in increased expression of phosphor-Akt in status epilepticus model in rats, which was accompanied with the attenuation of hippocampal cell death. Furthermore, administration of AG resulted in decreased expression of phosphor-JNK in pyramidal neurons of hippocampus after status epilepsy, which was also accompanied with the attenuation of hippocampal cell death, too. In addition, AG increased the Bcl-2/Bax ratio and inhibited caspase-3 activation. The data indicate that AG can function as a neuroprotective agent that inhibits apoptotic pathways. These effects may be mediated via activation of the PI3K/Akt pathway.
authors.affiliation: Department of Pediatrics, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Zhang
authors.forename: Guanglu
authors.initials: G
authors.lastname: Yang
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010862:Pilocarpine; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D054439:Ghrelin; C571124:Ghsr1a protein, rat; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D054440:Receptors, Ghrelin; D051028:bcl-2-Associated X Protein; D010862:Pilocarpine; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3