Experimental Kuru in the Spider Monkey

Abstract

The brains of 10 spider monkeys inoculated intracerebrally with brain suspension from kuru patients have been studied histologically and ultrastructurally. The animals were killed by perfusion of fixative from four to forty-one weeks after inoculation, when healthy and free of neurological signs. Definite histopathological changes had occurred as early as four weeks after inoculation, when moderate numbers of bi-nucleated neurons were found within the limbic cortex, striatum, the hypothalamus and amongst the Purkinje cells of the cerebellum. At later stages of incubation a moderate loss of neurons in the cerebral and cerebellar cortex and a mild to moderate proliferation of fibrous astrocytes here and also in the hypothalamus were the most striking features. None of our cases showed either status spongiosus or the generalized astrocytic proliferation and hypertrophy, characteristic of fully developed experimental kuru, in any region of the brain. The principal ultrastructural abnormalities consisted of the formation of membrane-bound intracytoplasmic vacuoles, predominantly within dendrites, and of concentric laminar arrays derived from the endoplasmic reticulum. The former were seen in all regions of the brain examined and at all stages of incubation. Concentric laminar arrays were confined to the cerebellar nodulus, where they were most numerous in dendrites and neuronal perikarya four weeks after inoculation. Both changes are interpreted as an indication that the kuru agent acts upon the plasma membrane from an early stage onwards and, by stimulating its growth, leads to the formation of complex, membrane-bounded vacuoles and to hyperplasia of the endoplasmic reticulum. The formation of vacuoles is further regarded as the first sign of status spongiosus on an ultrastructural level. Attention is drawn to the great similarities between the changes observed in the present material and those described in the brains of patients dying from kuru and of primates with fully developed experimental kuru. The significance of the relatively rapid spread of the kuru agent throughout the brain is discussed in relation to the concept of "slow virus" diseases.

Kuru

“…It is of utmost interest that as early as 1969, Lampert et al (having cited an earlier article by Arstila et al [88]) suggested that the spongiform change is somehow related to autophagy (84). Those pioneer data were confirmed by Beck et al (89), who also reported membrane lamination observed before full-blown pathology could be appreciated. From examination of the chimpanzee infected with the “K” kuru brain, the typical autophagic vacuoles were illustrated, but the process was not mentioned.…”

Kuru: A Journey Back in Time from Papua New Guinea to the Neanderthals’ Extinction

“…In the cerebral cortex, the spongiform change and intraneuronal vacuoles were the most prominent lesions, accompanied by a severe astrocytic gliosis. Binucleated neurons were prominent; the same type of neuronal lesions were also seen in the Spider monkey [ 112 ].…”

“…[ 144 ] and Beck et al . [ 112 ] found severe confluent spongiform change corresponded to typical membrane-bound vacuoles. Neurites showed dystrophic changes.…”

Cell fusion induced by scrapie and Creutzfeldt-Jakob virus-infected brain preparations.

“…Fusion occurring in vivo between a neuron and a glial cell has been noted electron microscopically in scrapie-infected mouse brain (3). Binucleated neurons occur in brains of patients with kuru (4,5) and in animals with experimental kuru (6,7), and multinucleated cells are commonly seen in cultured tissues from scrapie-infected animals (unpublished data). Together these observations suggested the possibility that the agents of subacute spongiform encephalopathies might promote cell fusion.…”