title: Cycloheximide inhibits neurotoxic responses induced by kainic acid in mice.
abstract: In the present study, we examined the effect of cycloheximide on various pharmacological responses induced by kainic acid (KA) administered intracerebroventricularly (i.c.v.) in mice. In a passive avoidance test, a 20-min cycloheximide (200mg/kg, i.p.) pretreatment prevented the memory impairment induced by KA. The morphological damage induced by KA (0.1microg) in the hippocampus was markedly concentrated in the CA3 pyramidal neurons and cycloheximide effectively prevented the KA-induced pyramidal cell death in CA3 hippocampal region. In immunohistochemical study, KA dramatically increased the phosphorylation of extracellular signal-regulated protein kinase (p-ERK), c-Jun N-terminal kinase 1 (p-JNK1), and calcium/calmodulin-dependent protein kinase II (p-CaMK II). Cycloheximide attenuated the increased p-ERK, p-JNK1, and p-CaMK II levels induced by KA. Furthermore, cycloheximide inhibited the increased c-Fos and c-Jun protein expression levels induced by KA in the hippocampus. The activation of microglia was detected in KA-induced CA3 cell death region by immunostaining with a monoclonal antibody against the OX-42. Cycloheximide inhibited KA-induced increase of OX-42 immunoreactivity. Our results suggest that the increased expression of the c-Fos, c-Jun, and phosphorylation of ERK, JNK1, and CaMK II proteins may play important roles in the memory impairment and the cell death in CA3 region of the hippocampus induced by i.c.v. KA administration in mice. Furthermore, the activated microglia may be related to phagocytosis of degenerated neuronal elements induced by KA.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, Kangwon-Do, 200-702, South Korea.
authors.forename: Han-Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Seong-Soo
authors.initials: SS
authors.lastname: Choi
authors.forename: Ki-Jung
authors.initials: KJ
authors.lastname: Han
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Han
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001362:Avoidance Learning / Q000187:drug effects; D051926:Basigin; D001798:Blood Proteins; D015153:Blotting, Western; D016923:Cell Death; D003513:Cycloheximide / Q000494:pharmacology*; D004347:Drug Interactions; D005110:Extracellular Space; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D048031:JNK Mitogen-Activated Protein Kinases; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011930:Reaction Time; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C497887:Bsg protein, mouse; C079432:Bsg protein, rat; D008562:Membrane Glycoproteins; D011500:Protein Synthesis Inhibitors; D051926:Basigin; D003513:Cycloheximide; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D007608:Kainic Acid