PATHOGENESIS OF TRIMETHYLTIN NEURONAL TOXICITY - ULTRASTRUCTURAL AND CYTOCHEMICAL OBSERVATIONS

Abstract

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 and pyriform cortex. The 1st subcellular alterations were multifocal collections of dense-cored vesicles and tubules and membrane-delimited vacuoles in the cytoplasm of the perikaryon and proximal dendride. Ultrastructural cytochemical examination revealed that the vesicles and tubules had acid phosphatase activity analogous 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 arose 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 microscopic or EM 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 were unique in neuronal cytopathology. GERL and autophagy played an important role in the pathogenesis of TMT-induced neuronal injury.