RESUMEN
The rat brain continues to mature after birth and is particularly vulnerable to developmental damage following perinatal insult. Borna disease virus (BDV) infection of postnatal day one (PND-1) rat brain causes a non-encephalitic, persistent infection associated with developmental neuroanatomical and behavioral abnormalities. To test the hypothesis that BDV infection during different brain developmental stages yields variable pathological and clinical disease sequelae, rats were examined for BDV-induced neuroanatomical and behavioral abnormalities following inoculation with BDV on PND-15, and the findings were compared to those resulting from inoculation on PND-1. Similar to rats inoculated with BDV on PND-1, PND-15 inoculated rats developed a persistent infection associated with body weight stunting, abnormal salt taste preference and hippocampal neuron degeneration. However, unlike rats infected with BDV on PND-1, PND-15 inoculated rats did not show signs of cerebellar hypoplasia or hyperactivity. Thus, the risk of BDV-induced damage to specific brain regions, and their associated behaviors, appears, in part, dependent upon the brain's developmental stage at time of BDV-infection. These studies provide evidence of the selective vulnerability of specific neuroanatomic regions and behaviors in developing nervous system to virus-induced damage.
Asunto(s)
Envejecimiento/fisiología , Animales Recién Nacidos/fisiología , Enfermedad de Borna/complicaciones , Daño Encefálico Crónico/virología , Encefalopatías/virología , Encéfalo/crecimiento & desarrollo , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Enfermedad de Borna/patología , Enfermedad de Borna/fisiopatología , Encéfalo/patología , Encéfalo/virología , Encefalopatías/patología , Encefalopatías/fisiopatología , Preferencias Alimentarias/fisiología , Ratas , Ratas Endogámicas Lew , Cloruro de Sodio , Gusto/fisiologíaRESUMEN
In rats infected as neonates, Borna disease virus (BDV) infection causes neuroanatomical, behavioral and physiological abnormalities without encephalitis. Neonatal infection with BDV provides a powerful model for studying the effects of virus replication on brain development without inflammation-induced brain damage. Here we report that neonatal BDV infection interfered with cerebellar development in the Lewis rat. Based on cerebellar cross-sectional area measurements, abnormal cerebellar growth was first noted between 7 and 14 days after infection. Reactive astrocytosis was evident by three days after infection, even without encephalitis, and even before identification of viral proteins in the cerebellum. While neonatal BDV infection caused a significant loss in granule cells, infected granule cells were not identified. BDV proteins were readily detected in the Purkinje cells. Thus, persistent BDV infection of Purkinje cells, but not granule cells, was associated with loss of granule cells during cerebellar development, in the absence of encephalitis.
Asunto(s)
Enfermedad de Borna/fisiopatología , Cerebelo/crecimiento & desarrollo , Edad de Inicio , Análisis de Varianza , Animales , Animales Recién Nacidos , Astrocitos/patología , Astrocitos/fisiología , Enfermedad de Borna/patología , Cerebelo/patología , Cerebelo/fisiopatología , Ingestión de Alimentos/fisiología , Ratas , Ratas Endogámicas LewRESUMEN
Newborn rats inoculated with Borna disease virus (BDV) develop a persistent, tolerant nervous system infection (PTI-NB), with no signs of encephalitis or Borna disease. We measured body weight, body length, taste preferences, and spontaneous locomotor activity over a 4-month period in PTI-NB and control rats. PTI-NB rats had decreased weight and length but not detectable disturbances in growth hormone and insulin-like growth factor-1 biosynthesis as compared to control rats. In single bottle taste acceptance tests, PTI-NB rats did not differ from controls and drank normal amounts of all solutions. When offered a choice of solutions in two-bottle taste preference tests, PTI-NB rats exhibited a normal preference for saccharin and a normal aversion for quinine, but an exaggerated preference for saline. At 1 and 4 months of age, PTI-NB rats were significantly more active than normal rats, although only 1-month-old PTI-NB rats had increased daytime activity. Thus, even in the absence of encephalitis, BDV infection of the PTI-NB rat is associated with a number of physiological and behavioral abnormalities.
Asunto(s)
Animales Recién Nacidos/fisiología , Enfermedad de Borna/patología , Enfermedad de Borna/fisiopatología , Enfermedades del Sistema Nervioso/patología , Enfermedades del Sistema Nervioso/fisiopatología , Animales , Peso Corporal , Virus de la Enfermedad de Borna , Preferencias Alimentarias , Hormonas/sangre , Actividad Motora , Ratas , Ratas Endogámicas Lew , Soluciones , GustoRESUMEN
We developed a mouse model of Borna disease to facilitate immunopathogenesis research by adaptation of Borna disease virus to mice through serial passage in mouse brain tissue. Borna disease virus replication, antibody production, inflammation, and Borna disease expression in several different strains of mice were examined.