Neurophysin in the brain and pituitary gland of normal and scrapie-affected sheep—II: Its occurrence in the cerebellum in dystrophic axon terminals with lysosome-lipofuscin accumulation: A possible anomaly of neuronal sulphur-protein metabolism

Abstract

Neurophysin (the protein present in neurosecretory granules of the posterior pituitary) has been demonstrated by immunofluorescence using a cross-species-reactive porcine neurophysin-II antiserum of high specificity in the cerebellum of sheep affected with the heredo-familial neurological disorder known as natural scrapie, but not in that of normal sheep. Neurophysin occurred in the granular and Purkinje cell layers, probably in axon terminals in the cerebellar glomeruli and on Purkinje cell bodies, in foci which on subsequent staining for neurosecretory material gave a ‘Gomori-positive’ reaction. Many foci of ‘Gomori-positive’ material did not show the presence of neurophysin. The cerebellum of a scrapie-affected sheep absorbed the specific neurophysin antibody from the antiserum almost as completely as did porcine neurophysin-II. Yellow autofluorescent bodies corresponding to lysosomes and lipofuscin, including giant forms, were greatly increased in the scrapie sheep. The data suggest that in scrapie there is an anomaly of neuronal protein metabolism affecting primarily the terminal axons of certain neurones with a prominent sulphur-protein metabolism. A slowly progressive and sequential terminal axon dystrophy ensues, during which neurophysin or a related compound appears in ectopic sites; the necessary basic metabolic pathways involved are probably widespread in cells outside the hypothalamo-neurohypophysial systems. The anomaly may represent acceleration of the normal process of ageing and be under single gene control. The applicability of the protein transcription error theory of senescence is discussed with particular reference to a possible anomaly of neuronal methionine metabolism with or without aberrant lysosome function.