Cytokine expression in the rat central nervous system following perinatal Borna disease virus infection

Borna disease virus (BDV) causes central nervous system (CNS) disease in several vertebrate species, which is frequently accompanied by behavioral abnormalities. In the adult rat, intracerebral (i.c.) BDV infection leads to immunomediated meningoencephalitis. In contrast, i.c. infection of neonates causes a persistent infection in the absence of overt signs of brain inflammation. These rats (designated PTI-NB) display distinct behavioral and neurodevelopmental abnormalities. However, the molecular mechanisms for these virally induced CNS disturbances are unknown. Cytokines play an important role in CNS function, both under normal physiological and pathological conditions. Astrocytes and microglia are the primary resident cells of the central nervous system with the capacity to produce cytokines. Strong reactive astrocytosis is observed in the PTI-NB rat brain. We have used a ribonuclease protection assay to investigate the mRNA expression levels of proinflammatory cytokines in different brain regions of PTI-NB and control rats. We show here evidence of a chronic upregulation of proinflammatory cytokines interleukin-6, tumor necrosis factor alpha, interleukins-1alpha, and -1beta in the hippocampus and cerebellum of the PTI-NB rat brain. These brain regions exhibited only a very mild and transient immune infiltration. In contrast, in addition to reactive astrocytes, a strong and sustained microgliosis was observed in the PTI-NB rat brains. Our data suggest that CNS resident cells, namely astrocytes and microglia, are the major source of cytokine expression in the PTI-NB rat brain. The possible implications of these findings are discussed.