Role of nicotinic acetylcholine receptors in the regulation of kainic acid-induced hippocampal cell death in mice.
Kainic acid (KA) is a well-known excitatory, neurotoxic substance. In mice, morphological damage of hippocampus induced by KA administered intracerebroventricularly (i.c.v.) was markedly concentrated on the CA3 pyramidal neurons. In the present study, the possible role of nicotinic acetylcholine receptors (nAchRs) in hippocampal cell death induced by KA (0.1 microg) administered i.c.v. was examined. Methyllycaconitine (MC; nAchRs antagonist, 20 microg) attenuated KA-induced CA3 pyramidal cell death. KA increased immunoreactivities (IRs) of phorylated extracellular signal-regulated kinase (p-ERK; at 30 min), p-CaMK II (at 30 min), c-Fos (at 2 h), c-Jun (at 2 h), glial fibrillary acidic protein (GFAP at 1 day), and the complement receptor type 3 (OX-42; at 1 day) in hippocampal area. MC attenuated selectively KA-induced p-CaMK II, GFAP and OX-42 IR in the hippocampal CA3 region. Our results suggest that p-CaMK II may play as an important regulator responsible for the hippocampal cell death induced by KA administered i.c.v. in mice. Reactive astrocytes, which was meant by GFAP IR, and activated microglia, which was meant by OX-42 IR, may be a good indicator for measuring the cell death in hippocampal regions by KA-induced excitotoxicity. Furthermore, it is implicated that niconitic receptors appear to be involved in hippocampal CA3 pyramidal cell death induced by KA administered i.c.v. in mice.
Lee
Han-Kyu
HK
Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, Kangwon-Do 200-702, South Korea.
Choi
Seong-Soo
SS
Han
Eun-Jung
EJ
Lee
Jin-Young
JY
Kwon
Min-Soo
MS
Shim
Eon-Jeong
EJ
Seo
Young-Jun
YJ
Suh
Hong-Won
HW
D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D007270:Injections, Intra-Articular / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000502:physiology*; D013194:Staining and Labeling / Q000379:methods
D039481:CD11b Antigen; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D016177:Macrophage-1 Antigen; D018733:Nicotinic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D007608:Kainic Acid; D000157:Aconitine