Persistent Borna Disease Virus (BDV) infection activates microglia prior to a detectable loss of granule cells in the hippocampus

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Journal of Neuroinflammation (Impact Factor: 5.41). 02/2008; 5(1):16. DOI: 10.1186/1742-2094-5-16
Source: PubMed


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.

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Available from: Mikhail V Pletnikov, Sep 10, 2015
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    • "Moreover, in Alzheimer's disease, characterization of fibrillar plaque development in brains of transgenic APP(SW) mice revealed that microglia are not only unable to clear amyloid-β deposits, but rather, contribute to plaque formation (Stalder et al., 2001; Wegiel et al., 2001). Additionally, microglia-derived chronic inflammation was shown to precede neuronal loss in neonatal borna disease virus (BDV) infection (Ovanesov et al., 2008). Collectively, these evident suggest that under intensive acute or chronic activation microglia fail to acquire the desired phenotype, lose their essential functions and turn actively deleterious, and thus cannot provide immune resolution and subsequent CNS protection . "
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    Frontiers in Cellular Neuroscience 04/2013; 7(article 34):34. DOI:10.3389/fncel.2013.00034 · 4.29 Impact Factor
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    • "Neonatal Borna disease virus infection in rats is associated with the activation of microglia and astrocytes and the loss of neurons in the dentate gyrus in the hippocampus, cortex and cerebellum (Gonzales-Dunia et al., 2000; Pletnikov et al., 2002; de la Torre, 2002). Ovanesov and colleagues were the first to find a significant increase in microglial activation and secondary neuronal loss (Ovanesov et al., 2008). Borna disease virus infection also affects astrocytes, which play an essential role in the maintenance of homeostasis in the CNS. "

    Psychiatric Disorders - Worldwide Advances, 10/2011; , ISBN: 978-953-307-833-5
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    • "In this respect, the gross structure of the hippocampus of a newborn rat approximately matches a third trimester human. Therefore, disordered macroscopic development of hippocampus, as complex function of microglia activation [30] [42], neurotrophin and cytokine signaling [28, 43–45], metabolic and oxidative stress ([36] [37] [39], also described in adult infected animals, [46] [47]) has direct relevance to in utero virus exposure in man. "
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    ABSTRACT: Borna disease (BD), caused by the neurotropic RNA virus, Borna Disease virus, is an affliction ranging from asymptomatic to fatal meningoencephalitis across naturally and experimentally infected warmblooded (mammalian and bird) species. More than 100 years after the first clinical descriptions of Borna disease in horses and studies beginning in the 1980's linking Borna disease virus to human neuropsychiatric diseases, experimentally infected rodents have been used as models for examining behavioral, neuropharmacological, and neurochemical responses to viral challenge at different stages of life. These studies have contributed to understanding the role of CNS viral injury in vulnerability to behavioral, developmental, epileptic, and neurodegenerative diseases and aided evaluation of the proposed and still controversial links to human disease.
    Interdisciplinary Perspectives on Infectious Diseases 02/2010; 2010:709791. DOI:10.1155/2010/709791
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