Neuropsychiatric - like disorders in transgenic mice expressing Borna disease virus phosphoprotein in the CNS

نویسندگان

  • T. Kobayashi
  • H. Taniyama
  • K. Tomonaga
  • P. Staeheli
  • M. Schwemmle
چکیده

Neurobehavioral disorder is a serious consequence of a number of viral infections in the central nervous system (CNS). A line of evidence has demonstrated that viral infections are associated with disturbances in neural functions that may be caused by alteration of the brain homeostasis. Here, we examined the role of viral persistent infection in neuropsychiatric disorders by generating a transgenic mouse expressing the 24 kDa-phosphoprotein (p24) of Borna disease virus (BDV) in the CNS. Under the control of the enhancer-promoter region of the glial Žbrillary acidic protein, we generated transgenic mice expressing BDV-p24 in the CNS. We demonstrated that BDV p24 interferes with the function of a multi-functional protein, HMGB1, in infected cells, suggesting some neurotropic effects of the p24 in infected CNSs. Glial expression of the transgene revealed a gradual deposit of the p24 in the CNS, especially at the neuropil in the hippocampus, without astrocytosis and neuronal degeneration. Behavioral analyses of the transgenic mice showed enhanced intermale aggressiveness and impairment of cognitive abilities. Furthermore, the transgenic mice showed progressive and marked decrease of synaptic density, which led to signiŽcant reduction in the brain-derived neurotropic factor. Thus, glial deposition or accumulation of BDV p24 may induce deleterious effects on the synaptic formation in the CNS, which may lead to neurobehavioral alterations. 49 Selective virus resistance conferred by expression of Borna disease virus nucleocapsid components T. Geib,1 M. Rauer,1 C. Sauder,1 S. Venturelli,1 C. Hässler,1 D. Schuppli,2 J. Götz,2 J. Hausmann,1 P. Staeheli,1 M. Schwemmle1 1. University of Freiburg (Freiburg, D) 2. University of Zürich (Zürich, CH)

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تاریخ انتشار 2005