Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 24, Issue 2, Pages 281-288Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2009.10.007
Keywords
H1N1 virus; Olfactory-nerve-transection; Tumor necrosis factor; Interleukin 1 beta; Olfactory bulb; Immunohistochemistry
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Funding
- Institute of Child Health and Development NIH [HD36520]
- National Institute of Neurological Disorders and Stroke [NS25378, NS31453]
- National Autonomous University of Mexico
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Mouse-adapted human influenza virus is detectable in the olfactory bulbs of mice within hours after intranasal challenge and is associated with enhanced local cytokine mRNA and protein levels. To determine whether signals from the olfactory nerve influence the unfolding of the acute phase response (APR), we surgically transected the olfactory nerve in mice prior to influenza infection. We then compared the responses of olfactory-nerve-transected (ONT) mice to those recorded in sham-operated control mice using measurements of body temperature, food intake, body weight, locomotor activity and immunohistochemistry for cytokines and the viral antigen, H1N1. ONT did not change baseline body temperature (Tb); however, the onset of virus-induced hypothermia was delayed for about 13 h in the ONT mice. Locomotor activity, food intake and body weights of the two groups were similar. At 15 h post-challenge fewer viral antigen-immunoreactive (IR) cells were observed in the olfactory bulb (OB) of ONT mice compared to sham controls. The number of tumor necrosis factor alpha (TNF alpha)- and interleukin 1 beta (IL1 beta)-IR cells in ONT mice was also reduced in the OB and other interconnected regions in the brain compared to sham controls. These results suggest that the olfactory nerve pathway is important for the initial pathogenesis of the influenza-induced APR. (C) 2009 Elsevier Inc. All rights reserved.
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