title: Role of gamma-aminobutyricacidB(GABA(B)) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus.
abstract: Kainic acid (KA) is well-known as an excitatory, neurotoxic substance. In mice, KA administered intracerebroventricularly (i.c.v.) lead to morphological damage of hippocampus expecially concentrated on the CA3 pyramidal neurons. In the present study, the possible role of gamma-aminobutyric acid B (GABA(B)) receptors in hippocampal cell death induced by KA (0.1 microg) administered i.c.v. was examined. 5-Aminovaleric acid (5-AV; GABA(B) receptors antagonist, 20 mug) reduced KA-induced CA3 pyramidal cell death. KA increased the phosphorylated extracellular signal-regulated kinase (p-ERK) and Ca(2+)/calmodulin-dependent protein kinase II (p-CaMK II) immunoreactivities (IRs) 30 min after KA treatment, and c-Fos, c-Jun IR 2 h, and glial fibrillary acidic protein (GFAP), complement receptor type 3 (OX-42) IR 1 day in hippocampal area in KA-injected mice. 5-AV attenuated KA-induced p-CaMK II, GFAP and OX-42 IR in the hippocampal CA3 region. These results suggest that p-CaMK II may play as an important regulator on hippocampal cell death induced by KA administered i.c.v. in mice. Activated astrocytes, which was presented by GFAP IR, and activated microglia, which was presented by the OX-42 IR, may be a good indicator for measuring the cell death in hippocampal regions by KA excitotoxicity. Furthermore, it showed that GABA(B) receptors appear to be involved in hippocampal CA3 pyramidal cell death induced by KA administered i.c.v. in mice.
authors.affiliation: Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Han Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Seo
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Choi
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kwon
authors.forename: Eon Jeong
authors.initials: EJ
authors.lastname: Shim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hong Won
authors.initials: HW
authors.lastname: Suh
mesh_terms: D021542:Amino Acids, Neutral / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000166:cytology* / Q000187:drug effects*; D007608:Kainic Acid / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*
chemical_list: D021542:Amino Acids, Neutral; D005904:Glial Fibrillary Acidic Protein; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018080:Receptors, GABA-B; C013809:5-aminovaleric acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D007608:Kainic Acid