Spongiform polioencephalomyelopathy caused by a murine retrovirus. II. Ultrastructural localization of virus replication and spongiform changes in the central nervous system.

The development of murine retrovirus induced spongiform polioencephalomyelopathy was studied sequentially by electron microscopy. During the initial 30 days, viral infection of the central nervous system, as evidenced by viral budding from membranes, was limited to the endothelial cells and pericytes. Viral particles were observed in the lumen of blood vessels, extracellular spaces and astrocytic endfeet surrounding blood vessels, but no morphological evidence of productive infection was found in astrocytes or neurons during early development of vacuolation. The earliest lesions in the neuropil consisted of swelling of astroglia followed by vacuolation, initially in axons and dendrites and later in neuronal and astrocytic soma, where vacuoles appeared to arise from dilated cisternae of the Golgi apparatus. Vacuoles contained only amorphous debris and fragments of membranes. Virions budding aberrantly into vacuoles were seen only in mice surviving beyond 35 days. Numerous reactive astrocytes were observed, but inflammatory cells were absent. The ultrastructural changes were remarkably similar to those described in scrapie, Kuru, and Creutzfeldt-Jakob disease.

Murine neurotropic retrovirus spongiform polioencephalomyelopathy: acceleration of disease by virus inoculum concentration.

A 10-fold reduction in the incubation period of murine neurotropic retrovirus spongiform polioencephalomyelopathy was effected by a 1,000-fold concentration of the cloned virus inoculum.

Presence of displaced neural elements within rat cerebellar fissures.

Clusters of neural tissue have been observed within the cerebellar fissures of normal and experimentally treated albino rats and hooded rats, between the ages of 5 and 90 days. The observations of these intra-fissural clusters were made in conjunction with several series of experiments dealing with the effects of various treatments on cerebellar morphogenesis. More important is the fact that similar displaced clusters are present in normal, untreated animals. Clusters can show a considerable variation in size, ranging from a few closely packed cells, to clusters with many cells completely occupying the area between the two folial surfaces, The clusters consist of immature or mature granule cells, depending on the age. With increasing age a well-developed neuropil is seen with bundles of parallel fibers coursing among the granule cells, along with occasional Bergmann glial fibers, capillaries and pericytes. Synaptic contacts, possibly granule cells, are present within the cluster. The continued differentiation of the cells in the clusters is exemplified by the observation of a mossy fiber terminal at the base of a cluster. Connecting each cluster with the nearby parenchyma is a stalk consisting of granule cells, Bergmann glial fibers, and neurites. The basal lamina of the folial surface is interrrupted at this point. The presence of these clusters implies a failure of normal morphogenetic and migrational control mechanisms. Importantly, the cells of the clusters continue to differentiate and to make synaptic connections, despite their abnormal location.

Presence of radial glia in foetal mouse cerebellum.

The ventricular layer (VL) of foetal mouse cerebellum at days 13--15 of gestation was studied by light and electron microscopy. In Golgi-stained material, round or ovoid cells are located in the VL. These cells have ascending processes, which extend to the pial surface. Ultrastructurally, the ascending processes are electron-lucent, contain microfilaments, some smooth endoplasmic reticulum and scant free ribosomes. They appear to be immature glial processes, oriented radially away from the ventricle. The perikarya of these glial cells lie either in the ventricular or subventricular zones. Juxtaposed along the length of these radially oriented glial processes are unidentified cells, some of which are attached to the immature glial fibres by puncta adhaerentia. These cells are elongated or ovoid with a thin rim of cytoplasm containing few organelles. These unidentified cells may represent neuroblasts (Purkinje cells, Golgi cells, cells of the deep cerebellar nuclei) or glioblasts, (precursors of astrocytes and/or oligodendrocytes) at very early stages of development.

Lack of evidence for glial cells originating from the external granular layer in mouse cerebellum.

In 25 day mice cerebella, a quantitative electron microscopic analysis showed that glial cells were not seen among 749 cells counted in the molecular layer. Likewise, a light microscopic autoradiographic study showed that labelled oligodendroglia and/or astroglia in the cerebellum were not derived from the external granular layer (EGL). Previous claims, that these cells derived from the EGL, may have arisen because other cell types, i.e., endothelial cells, pericytes, microglia, and other ectopic granule cells may have been misidentified as oligodendroglia and/or astroglia. It seems likely that the EGL is a unique germinal cell layer in the mammalian nervous system because it gives rise only to neurons, whereas cerebellar astrocytes and oligodendrocytes are derived from the subventricular layer of the fourth ventricle, as first suggested by Cajal in 1911.

Prenatal development of Bergmann glial fibres in rodent cerebellum.

The external granular and molecular layers in the foetal cerebellar cortex of mice and rats were examined by electron microscopy for the presence of Bergmann glial fibres. Morphologically distinct Bergmann fibres were observed at embryonic day E 15 in the mouse and at E 17 in the rat. Even at prenatal stages of development these fibres have a considerable degree of cytological differentiation which permits their identification as glial elements. The glial fibres contain numerous microfilaments, some smooth endoplasmic reticulum, a few mitochondria and scant free ribosomes. They penetrate the molecular and external granular layers radially and terminate with endfeet at the cerebellar surface. The proliferative cells of the external granular layer possess cytoplasmic processes which are oriented randomly, do not have endfeet, and are morphologically distinct from the Bergmann fibres with which they intermingle. In conclusion, immature Bergmann glial cells are present well before birth in the rodent cerebellum.

Retrograde amnesia: electroconvulsive shock effects after termination of rapid eye movement sleep deprivation.

Mice that were deprived of rapid eye movement sleep for 2 days immediately after one-trial training in an inhibitory avoidance task and were given an electroconvulsive shock after deprivation displayed retrograde amnesia on a retention test given 24 hours later. Electroconvulsive shock produced no amnesia in comparable groups of animals that were not deprived of rapid eye movement sleep.