In vivo acute treatment with trimethyltin chloride causes neuronal degeneration in the murine olfactory bulb and anterior olfactory nucleus by different cascades in each region.
Our earlier study demonstrated that in vivo acute treatment with trimethyltin chloride (TMT) produces severe neuronal damage in the dentate gyrus and cognition impairment in mice. In the present study, we assessed whether TMT was capable of causing neuronal degeneration in the olfactory bulb (OB) and anterior olfactory nucleus (AON) of the mouse brain. An intraperitoneal injection of TMT at the dose of 2.8 mg/kg led to a dramatic increase in the number of degenerating cells, which were reactive with antibody against single-stranded DNA, in the granule cell layer (GCL) of the OB and AON 1 day and 2 days later, respectively. TMT treatment produced a marked translocation of phospho-c-Jun-N-terminal kinase from the cytoplasm to the nucleus in the AON. Expectedly, a marked increase in phospho-c-Jun-positive cells was seen in the AON after the treatment. In addition to the AON, the mitral cell layer of the olfactory bulb showed the presence of phospho-c-Jun-positive cells after the treatment. However, the GCL had no cells positive for either phospho-c-Jun-N-terminal kinase or phospho-c-Jun at any time after the treatment with TMT. Similarly, TMT-induced nuclear translocation of the lysosomal enzyme deoxyribonuclease II was seen in the AON, but not in the GCL. On the other hand, TMT elicited the expression of activated caspase 3 in the GCL but not in the AON. Taken together, our results suggest that TMT is capable of causing neuronal degeneration in the murine OB and AON through different cascades in the two structures.
Kawada
Koichi
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University Hirakata, Osaka, Japan.
Yoneyama
Masanori
M
Nagashima
Reiko
R
Ogita
Kiyokazu
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D066298:In Vitro Techniques; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000473:pathology*; D009830:Olfactory Bulb / Q000473:pathology*; D009833:Olfactory Pathways / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000494:pharmacology*
D016755:Proto-Oncogene Proteins c-jun; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride; D048670:MAP Kinase Kinase 4; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II; D053148:Caspase 3