Pathogenesis of trimethyltin neuronal toxicity. Ultrastructural and cytochemical observations.
The ultrastructural cytopathologic and cytochemical effects of trimethyltin (TMT) neurotoxicity were delineated in hippocampal and pyriform neurons of acutely intoxicated adult rats. TMT produced neuronal necrosis that preferentially involved hippocampal formation pyriform cortex. The first subcellular alterations were multifocal collection of dense-cored vesicles and tubules and membrane-delimited vacuoles in the cytoplasm of the perikaryon and proximal dendrite. Ultrastructural cytochemical examination revealed that the vesicles and tubules had acid phosphatase activity analagous to Golgi-associated endoplasmic reticulum (GERL). Shortly after the appearance of the GERL-like vesicles and tubules, autophagic vacuoles and polymorphic dense bodies accumulated in the neuronal cytoplasm. Some dense bodies appeared to arise from the dense-cored tubules. Neuronal necrosis was characterized by increased electron density of the cytoplasm and large, electron-dense intranuclear masses. Alterations of mitochondria and other organelles were not observed in the early stages of cell injury. No light- or electron-microscopic alterations were found in liver or kidney. Comparable subcellular alterations were observed in adult and neonatal rats chronically intoxicated with TMT. A series of other trialkyl and tricyclic tins and dimethyltin did not produce similar pathologic findings. The GERL-like accumulations are unique in neuronal cytopathology. These findings suggests that GERL and autophagy play an important role in the pathogenesis of TMT-induced neuronal injury.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003593:Cytoplasm / Q000473:pathology / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D005260:Female; D008297:Male; D009336:Necrosis; D009422:Nervous System Diseases / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D009947:Organotin Compounds / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D009947:Organotin Compounds; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds