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 se veral vertebrate species, which is frequently accompanied by behavioral abn ormalities. In the adult rat, intracerebral (i.c.) BDV infection leads to i mmunomediated meningoencephalitis. In contrast, i.c. infection of neonates causes a persistent infection in the absence of overt signs of brain inflam mation. These rats (designated PTI-NB) display distinct behavioral and neur odevelopmental abnormalities. However, the molecular mechanisms for these v irally induced CNS disturbances are unknown. Cytokines play an important ro le in CNS function, both under normal physiological and pathological condit ions. Astrocytes and microglia are the primary resident cells of the centra l nervous system with the capacity to produce cytokines. strong reactive as trocytosis is observed in the PTI-NB rat brain. We have used a ribonuclease protection assay to investigate the mRNA expression levels of proinflammat ory cytokines in different brain regions of PTI-NB and control rats. We sho w here evidence of a chronic upregulation of proinflammatory cytokines inte rleukin-6, tumor necrosis factor alpha, interleukins-1 alpha, and -1 beta i n the hippocampus and cerebellum of the PTI-NB rat brain. These brain regio ns exhibited only a very mild and transient immune infiltration. In contras t, in addition to reactive astrocytes, a strong and sustained microgliosis was observed in the PTI-NB rat brains. Our data suggest that CNS resident c ells, namely astrocytes and microglia, are the major source of cytokine exp ression in the PTI-NB rat brain. The possible implications of these finding s are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.