title: Persistent Borna disease virus infection of neonatal rats causes brain regional changes of mRNAs for cytokines, cytokine receptor components and neuropeptides.
abstract: Borna disease virus (BDV) replicates in brain cells. The neonatally infected rat with BDV exhibits developmental-neuromorphological abnormalities, neuronal cytolysis, and multiple behavioral and physiological alterations. Here, we report on the levels of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), IL-1 receptor type I (IL-1RI), IL-1 receptor 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 BDV inoculation. The data show that cytokine and neuropeptide mRNA components are abnormal and differentially modulated in brain regions. IL-1beta, TNF-alpha and TGF-beta1 mRNA levels were up-regulated in all brain regions following BDV inoculation. The same cerebellar samples from BDV-infected animals exhibited the highest levels of IL-1beta, IL-1Ra, TNF-alpha, IL-1RI, and IL-1R AcP II mRNA expression. The profiles of IL-1beta, IL-1Ra, TNF-alpha, and TGF-beta1 mRNA induction in the cerebellar samples were highly intercorrelated, indicating an association among cytokine ligand mRNAs. Cytokine mRNA induction was differentially up-regulated among brain regions, except for TGF-beta1. Specificity of transcriptional changes in response to BDV infection is also suggested by the up-regulation of cytokine and neuropeptide Y mRNAs associated with down-regulation of pro-opiomelanocortin, and with no change of IL-1R AcPI, dynorphin and leptin receptor mRNAs in the same 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 cytokines may play a role in the neuropathophysiology of neonatally BDV-infected rats.
authors.affiliation: Division of Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark, USA. CplataSa@prius.jnj.com
authors.forename: C R
authors.initials: CR
authors.lastname: Plata-Salamán
authors.forename: S E
authors.initials: SE
authors.lastname: Ilyin
authors.forename: D
authors.initials: D
authors.lastname: Gayle
authors.forename: A
authors.initials: A
authors.lastname: Romanovitch
authors.forename: K M
authors.initials: KM
authors.lastname: Carbone
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001890:Borna Disease / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D018121:Receptors, Cytokine / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000235:genetics; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D009479:Neuropeptides; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha