An integrated study of the morphological and gross-elemental consequences of methyl mercury intoxication in rats, with particular attention on the cerebellum.

Methylmercury accumulates in the kidney and liver of rats, but fairly selectively damages the cerebellum, resulting in the clinical symptoms of neurological ataxia after prolonged exposures. Within the cerebellum, morphological examination indicated that the small granule cells beneath the Purkinje layer are especially susceptible to the toxin, showing signs of pyknosis during the phase of locomotory disability, whilst the large Purkinje cells are relatively resistant to cytotoxic injury. Flame photometric and electron probe X-ray microanalysis (EPXMA) of digested samples of the major organs failed to detect any significant changes in the Na, K, Ca, Mg, S and P concentrations of the organs, including the cerebellum, at intervals after methylmercury administration by either gastric gavage or via the drinking water. It was suggested that if the lesion within the cerebellum is restricted, as the morphological evidence suggests, to a small cohort of functionally important granule cells, then it may be difficult to detect elemental changes within this subpopulation against the compositionally unaltered majority of cerebellar cells and their extracellular spaces. To identify and compositionally characterize the injured cells requires electron probe X-ray microanalysis of frozen sections, or fractured bulk samples. The deep-seated nature of the 'target cells' within the cerebellum presents formidable cryopreparative problems.