Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice

Wataru Kamitani, Etsuro Ono, Saori Yoshino, Tsutomu Kobayashi, Satoshi Taharaguchi, Byeong Jae Lee, Makiko Yamashita, Takeshi Kobayashi, Minoru Okamoto, Hiroyuki Taniyama, Keizo Tomonaga, Kazuyoshi Ikuta

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52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8969-8974
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number15
DOIs
Publication statusPublished - Jul 22 2003
Externally publishedYes

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