[Abstract Title]. - Society for Neuroscience

NS25378 by JM Krueger
Title: Influenza virus inoculation in male mice increases interleukin-1 beta- and tumor necrosis
factor alpha-immunoreactive cells in the piriform cortex, olfactory tubercle and central amygdala
Authors: *L. CHURCHILL 1,2 , V. LEYVA-GRADO 1 , T. J. WILLIAMS 1 , P. TAISHI 1 , J. A.
MAJDE 1 , J. M. KRUEGER 1 ;
1 Dept VCAPP, 2 Washington State Univ., Pullman, WA
Abstract: During influenza virus infections, the cytokines interleukin-1 beta (IL1β) and tumor
necrosis factor alpha (TNFα) increase as part of the acute phase response. We have demonstrated
that viral replication intermediates increase in the olfactory bulb (OB) as early as 4 h after nasal
inoculation of C57Bl/6 male mice with live, mouse-adapted PR8/H1N1 influenza virus and
continue to be present at 15 h. The mice respond to the viral infection with hypothermia
beginning at 11-13 h after viral challenge. We have also demonstrated that cytokineimmunoreactive
(IR) cells increase within the external plexiform layer (EPL) of the OB at 15 h
after inoculation of live PR8 virus relative to boiled (heat-inactivated) PR8. In this study we
hypothesize that the cytokine-IR cells in the EPL will project to the piriform cortex, olfactory
tubercle and central amygdala to stimulate cytokine-IR cells. Preliminary data indicate that
cutting of the olfactory nerve delays the onset of hypothermia suggesting that the entry of the
influenza virus through the olfactory nerve is important in the acute phase response. Antibody
specificity for TNFα and IL1β was verified by the loss of specific staining in IL1β- and TNFαknockout
mice as well as by preabsorbtion with the appropriate mouse recombinant proteins.
Western blot analyses demonstrated that the proform for IL1β and TNFα was labeled in the
olfactory bulb and preabsorbed with the appropriate mouse recombinant proteins. Live PR8
inoculation increased the number of IL1β- and TNFα-IR cells in the piriform cortex, olfactory
tubercle and central amygdala (brain regions that receive innervation from the olfactory bulb) at
15 h but not by 10 h which was prior to the physiological response to the virus. Double labeling
with the neuronal nuclear protein marker, NeuN, indicated that the IL1β- and TNFα-IR were
present in neurons in the piriform cortex, olfactory tubercle and central amygdala. These data
suggest that the viral replication intermediates present in the olfactory bulb after the influenza
virus inoculation may activate cytokine production in neurons that communicate with other
centrally localized neurons to induce cytokines in these neurons as well.
Disclosures: L. Churchill, None; V. Leyva-Grado, None; T.J. Williams, None; P. Taishi,
None; J.A. Majde, None; J.M. Krueger, None.
Poster
285. Sleep: Molecular, Cellular and Pharmacology I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm