Neonatal Borna disease virus infection in the rat causes a loss of Purkinje cells in the cerebellum

Abstract

Viral insults that occur during early postnatal periods, can affect neuronal systems which exhibit signi®cant postnatal development, such as the cerebral cortex and cerebellum. Borna disease virus (BDV) is a single-strand RNA virus which replicates in the nervous system of many species after experimental inoculation and causes acute neurological disease. Neonatal rats infected with BDV do not mount an aggressive response to the virus like their adult counterparts, but instead develop a persistent BDV infection with less overt clinical sequelae. Recently, the cerebellum, a neural structure associated with regulation of motor behavior, and perhaps with higher cognitive functions, has been demonstrated to be a target of neonatal BDV infections in rats (Bautista et al, 1995). In the present study neonatal rats were infected with BDV and their cerebella were analyzed histologically and immunohistochemically at 7 months of age. The cerebella of infected animals were reduced in size but normal foliation and laminar organization was present. However, as visualized with immunohistochemistry for the Purkinje cell-speci®c antigen calbindin, there were numerous gaps within the Purkinje cell layer and in the molecular layer which contains the Purkinje cell dendritic trees. We estimated the number of Purkinje cells and found there was an approximately 75% loss of PC in adult rats neonatally infected with BDV. These results suggest that neonatal BDV infection may either (1) target the PC and cause the death of these cells directly or (2) acts indirectly by triggering an immune response which is then responsible for the loss of these cells.

Calbindin D28k distribution in neurons and reactive gliosis in cerebellar cortex of natural Rabies virus–infected cattle

“…27 Previous reports of different viral encephalitides from HIV encephalitis in humans 30 to neonatal Borna disease infection in rats, 9 and experimental infection of rabies in mice, 40 or aging in dogs, 36 postulate a relationship between loss of CbD28k immunoreactivity and dysfunctions in GABAergic neurotransmission.…”

“…30 In rats, experimental neonatal Borna disease viral infection induces a loss of cerebellar Purkinje cells that is easily detected using CbD28k as a specific marker of these neurons. 9 In scrapie-affected adult sheep, the assessment of CbD28k, parvalbumin, and calretinin also demonstrate that the use of these CaBPs could be a valuable diagnostic tool to identify specific alterations in this encephalopathy, showing that the cerebellar cortex-mainly the Purkinje cell layer-is the sole CNS region with positive CbD28k immunolabeling, although this immunoreactivity is not affected by scrapie. 38,42 The purpose of the present work was to describe the distribution of CbD28k immunoreactivity in the cerebellar cortex of RABV-infected cattle, and to characterize this antibody as a specific tool to detect alterations in this CaBP and therefore likely changes in calcium homeostasis in the cerebellar cortex during RABV-induced neurodegeneration.…”

Histopathology and the detection of avian bornavirus in the nervous system of birds diagnosed with proventricular dilatation disease

“…It was unclear from the reports accompanying these samples whether any of these PDD cases demonstrated significant motor deficits. It is of interest to note that the cerebellum is targeted in BDV infection of neonatal rats (Eisenman et al, 1999), although not in the natural disease of horses (Ludwig & Bode 2000). Thus neonatal rats infected with BDV develop a persistent infection.…”

The Central Nervous System Inflammatory Response to Neurotropic Virus Infection Is Peroxynitrite Dependent

“…In both cases, a persistent BDV infection with little evidence of overt disease ensues (6, 7). In the developing rat, BDV infection causes a slow, progressive loss of Purkinje cells, with limited neuropathological and behavioral changes and little evidence of CNS inflammation (9,10). On the other hand, the acute Borna disease seen in immunocompetent adult rats is associated with extensive CD4 T cell-dependent CNS inflammation and BDV-specific CD8 T cell activity (11)(12)(13)(14)(15).…”