Recent studies on the trimethyltin actions in central nervous systems.
Trimethyltin (TMT) is a toxic organotin compound that produces injury to the central nervous systems of mammals. Recently, high-dose TMT (2.8 mg/kg) has been shown to produce neurodegeneration and subsequent neurogenesis specifically in the hippocampal dentate gyrus of mice, indicating that mice injected with TMT serve as a useful in vivo model to study neurogenesis as well as neurodegeneration in this brain region. In addition, gene-engineered mice have allowed research to focuse on the mechanisms of TMT toxicity. These studies have revealed the involvement of stannin, nuclear factor kappa B (NF-kappaB), presenilin-1, apolipoprotein E, and pituitary adenylyl cyclase-activating polypeptide (PACAP) in TMT toxicity and suggested the relationship between genetic mutations and neuronal susceptibility to degeneration. In this review, we briefly summarize the previous studies and discuss the current status of research on TMT.
Shintani
Norihito
N
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita City, Japan. shintani@phs.osaka-u.ac.jp
Ogita
Kiyokazu
K
Hashimoto
Hitoshi
H
Baba
Akemichi
A
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D009410:Nerve Degeneration / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D014298:Trimethyltin Compounds / Q000633:toxicity*
D001057:Apolipoproteins E; D016328:NF-kappa B; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D053764:Presenilin-1; D014298:Trimethyltin Compounds; C046488:trimethyltin; C075692:stannin