Spongy degeneration in the zitter rat: ultrastructural and immunohistochemical studies

Pathological changes in the grey matter of the zitter rat were examined by electron microscopy and immunohistochemistry to investigate the pathogenesis of spongy degeneration. Vacuole formation was first detected in the pons and the outer thalamus at 2 weeks of age. The vacuoles arose from the periaxonal or inter-myelinic spaces as well as the cytoplasm of some oligodendrocytes or astrocytes. With increasing age, some dendrites and the cytoplasm of neurons developed an electron lucent area with sparse organelles and the vacuoles occasionally fused together. Although spongy degeneration gradually extended to the entire CNS, no inflammatory or phagocytotic cell infiltration and no viral particles were detected. Glial fibrillary acidic protein immunoreactivity increased transiently in the vacuolated areas from 2 to 15 weeks of age (maximal at 7 weeks of age). Although zitter rats older than 65 weeks showed some reactive astrocytes in vacuolated areas, their numbers and the intensity of immunostaining decreased with advanced vacuolation suggesting astrocytic hypofunction in response to tissue damage. Immunoreactivity for synaptophysin was weaker in the zitter rats than in the control rats throughout the observation period, which suggested that synapse formation was disturbed in the zitter rats, probably due to a combination of hypomyelination and vacuole formation in the grey matter. These findings suggest that an unknown genetic abnormality, probably related to cell membrane biosynthesis or cell-to-cell interactions, produces both hypomyelination and spongy degeneration in the zitter rat.