Possible role of the glycogen synthase kinase-3 signaling pathway in trimethyltin-induced hippocampal neurodegeneration in mice.
Trimethyltin (TMT) is an organotin compound with potent neurotoxic effects characterized by neuronal destruction in selective regions, including the hippocampus. Glycogen synthase kinase-3 (GSK-3) regulates many cellular processes, and is implicated in several neurodegenerative disorders. In this study, we evaluated the therapeutic effect of lithium, a selective GSK-3 inhibitor, on the hippocampus of adult C57BL/6 mice with TMT treatment (2.6 mg/kg, intraperitoneal [i.p.]) and on cultured hippocampal neurons (12 days in vitro) with TMT treatment (5 µM). Lithium (50 mg/kg, i.p., 0 and 24 h after TMT injection) significantly attenuated TMT-induced hippocampal cell degeneration, seizure, and memory deficits in mice. In cultured hippocampal neurons, lithium treatment (0-10 mM; 1 h before TMT application) significantly reduced TMT-induced cytotoxicity in a dose-dependent manner. Additionally, the dynamic changes in GSK-3/β-catenin signaling were observed in the mouse hippocampus and cultured hippocampal neurons after TMT treatment with or without lithium. Therefore, lithium inhibited the detrimental effects of TMT on the hippocampal neurons in vivo and in vitro, suggesting involvement of the GSK-3/β-catenin signaling pathway in TMT-induced hippocampal cell degeneration and dysfunction.
Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju, Republic of Korea.
Juhwan
J
Kim
Miyoung
M
Yang
Sung-Ho
SH
Kim
Jong-Choon
JC
Kim
Hongbing
H
Wang
Taekyun
T
Shin
Changjong
C
Moon
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000201:enzymology*; D014298:Trimethyltin Compounds / Q000494:pharmacology*
D014298:Trimethyltin Compounds; C046488:trimethyltin; D038362:Glycogen Synthase Kinase 3