Persistent Borna disease virus infection of neonatal rats causes brain regional changes of mRNAs for cytokines, cytokine receptor components and neuropeptides

Borna disease virus (BDV) replicates in brain cells. The neonatally infecte d rat with BDV exhibits developmental-neuromorphological abnormalities, neu ronal cytolysis, and multiple behavioral and physiological alterations. Her e, we report on the levels of interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 1 (TGF-beta 1), IL-1 receptor type I (IL-1RI), IL-1 rec eptor accessory protein (IL-1R AcP) I and II, glycoprotein 130, and various neuropeptide mRNAs in the cerebellum, parieto-frontal cortex, hippocampus and hypothalamus of BDV-infected rats at 7 and 28 days postintracerebral BD V inoculation. The data show that cytokine and neuropeptide mRNA components are abnormal and differentially modulated in brain regions. IL-1 beta, TNF -alpha and TGF-beta 1 mRNA levels were up-regulated in all brain regions fo llowing BDV inoculation. The same cerebellar samples from BDV-infected anim als exhibited the highest levels of IL-1 beta, IL-1Ra, TNF-alpha, IL-1RI, a nd IL-1R AcP II mRNA expression. The profiles of IL-1 beta, IL-1Ra, TNF-alp ha, and TGF-beta 1 mRNA induction in the cerebellar samples were highly int ercorrelated, indicating an association among cytokine ligand mRNAs. Cytoki ne mRNA induction was differentially upregulated among brain regions, excep t for TGF-beta 1. Specificity of transcriptional changes in response to BDV infection is also suggested by the up-regulation of cytokine and neuropept ide Y mRNAs associated with down-regulation of pro-opiomelanocortin, and wi th no change of IL-1R AcP I, dynorphin and leptin receptor mRNAs in the sam e brain region samples. Other data also show a differential mRNA component modulation in distinct brain regions obtained from the same rats depending on the stage of BDV infection. The conclusion of these studies is that cyto kines may play a role in the neuropathophysiology of neonatally BDV-infecte d rats. (C) 1999 Elsevier Science Inc.