title: Persistent Borna Disease Virus (BDV) infection activates microglia prior to a detectable loss of granule cells in the hippocampus.
abstract: Neonatal Borna Disease Virus (BDV) infection in rats leads to a neuronal loss in the cortex, hippocampus and cerebellum. Since BDV is a non-lytic infection in vitro, it has been suggested that activated microglia could contribute to neuronal damage. It is also conceivable that BDV-induced cell death triggers activation of microglia to remove cell debris. Although an overall temporal association between neuronal loss and microgliosis has been demonstrated in BDV-infected rats, it remains unclear if microgliosis precedes or results from neuronal damage. We investigated the timing of microglia activation and neuronal elimination in the dentate gyrus (DG) of the hippocampus. We found a significant increase in the number of ED1+ microglia cells as early as 10 days post infection (dpi) while a detectable loss of granule cells of the DG was not seen until 30 dpi. The data demonstrate for the first time that a non-lytic persistent virus infection of neurons activates microglia long before any measurable neuronal loss.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ovanesovm@janelia.hhmi.org
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Ovanesov
authors.forename: Krisztina
authors.initials: K
authors.lastname: Moldovan
authors.forename: Kimberly
authors.initials: K
authors.lastname: Smith
authors.forename: Michael W
authors.initials: MW
authors.lastname: Vogel
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pletnikov
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D001890:Borna Disease / Q000276:immunology* / Q000473:pathology; D001921:Brain; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000473:pathology*; D005260:Female; D005911:Gliosis / Q000209:etiology / Q000276:immunology; D007267:Injections; D017628:Microglia / Q000737:chemistry / Q000276:immunology* / Q000821:virology; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins