title: Characterization of temporal expressions of FOXO and pFOXO proteins in the hippocampus by kainic acid in mice: involvement of NMDA and non-NMDA receptors.
abstract: In the present study, we characterized the expression and role of forkhead box O (FoxO3a) in kainic acid (KA)-induced hippocampal neuronal cell death. FoxO3a and pFoxO3a expression in the CA1, CA2, and dentate gyrus regions in the hippocampus increased 0.5 and 1 h after intracerebroventricular administration of KA. In addition, both FoxO3a and pFoxO3a expression in the hippocampal CA3 region increased significantly and equally for 1 h but decreased gradually for 24 h after KA administration. In particular, the KA-induced increases in FoxO3a and pFoxO3a expression in the hippocampal CA3 region were inhibited by pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801, dizocilpine, 1 µg/5 µl) or a non-NMDA receptor antagonist (CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione, 0.5 µg/5 µl). Furthermore, dizocilpine and CNQX produced a neuroprotective effect against KA-induced neuronal death in the CA3 region of the hippocampus. Our results suggest that FoxO3a and pFoxO3 expression is upregulated by KA. Both FoxO3a and pFoxO3a expression appear to be responsible for KA-induced neuronal death in the CA3 region of the hippocampus.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Okchun-Dong, Chuncheon, Kangwon-Do, 200-702, Republic of Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Okchun-Dong, Chuncheon, Kangwon-Do, 200-702, Republic of Korea.|#81 Biotechnology Incubating Center, Institute for Stem Cell and Regenerative Medicine in Kangstem Biotech, Seoul National University, Seoul, 151-742, Republic of Korea.
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Sim
authors.affiliation: Department of Pharmacology, College of Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.
authors.forename: Jin-Koo
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, 200-702, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Okchun-Dong, Chuncheon, Kangwon-Do, 200-702, Republic of Korea. hwsuh@hallym.ac.kr.
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D000071316:Forkhead Box Protein O3 / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; D007608:Kainic Acid
keywords: CNQX; FoxO; Hippocampus; Kainic acid; MK-801