title: Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice.
abstract: One hypothesis for the etiology of behavioral disorders is that infection by a virus induces neuronal cell dysfunctions resulting in a wide range of behavioral abnormalities. However, a direct linkage between viral infections and neurobehavioral disturbances associated with human psychiatric disorders has not been identified. Here, we show that transgenic mice expressing the phosphoprotein (P) of Borna disease virus (BDV) in glial cells develop behavioral abnormalities, such as enhanced intermale aggressiveness, hyperactivity, and spatial reference memory deficit. We demonstrate that the transgenic brains exhibit a significant reduction in brain-derived neurotrophic factor and serotonin receptor expression, as well as a marked decrease in synaptic density. These results demonstrate that glial expression of BDV P leads to behavioral and neurobiological disturbances resembling those in BDV-infected animals. Furthermore, the lack of reactive astrocytosis and neuronal degeneration in the brains indicates that P can directly induce glial cell dysfunction and also suggests that the transgenic mice may exhibit neuropathological and neurophysiological abnormalities resembling those of psychiatric patients. Our results provide a new insight to explore the relationship between viral infections and neurobehavioral disorders.
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kamitani
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ono
authors.forename: Saori
authors.initials: S
authors.lastname: Yoshino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Taharaguchi
authors.forename: Byeong-Jae
authors.initials: BJ
authors.lastname: Lee
authors.forename: Makiko
authors.initials: M
authors.lastname: Yamashita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Minoru
authors.initials: M
authors.lastname: Okamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniyama
authors.forename: Keizo
authors.initials: K
authors.lastname: Tomonaga
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D000818:Animals; D001890:Borna Disease / Q000503:physiopathology / Q000523:psychology / Q000821:virology; D001891:Borna disease virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000209:etiology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008959:Models, Neurological; D009422:Nervous System Diseases / Q000209:etiology / Q000473:pathology / Q000821:virology; D009457:Neuroglia / Q000502:physiology* / Q000821:virology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D010750:Phosphoproteins; D014764:Viral Proteins