[Abstract Title]. - Society for Neuroscience

Support: NSF grant 0549987 to TD
HDRF grant 6-008 to TD
Title: Regulation of stress induced neuroinflammatory factors by norepinephrine and
corticosterone
Authors: *P. BLANDINO, C. J. BARNUM, B. S. LANKOW, S. ZOLA, T. DEAK;
Dept Behav Neurosci, SUNY-Binghamton, Binghamton, NY
Abstract: We recently reported that exposure to an acute session of footshock increased IL-1
and CD14 mRNA in the hypothalamus, while CD200 receptor (CD200R) mRNA was downregulated
in the same tissue. Previous data have also shown that the noradrenergic antagonist
propranolol blocked the increase in hypothalamic IL-1 protein, and that adrenalectomy
augmented hypothalamic IL-1 protein in response to stress. However, it remains unclear whether
norepinephrine and corticosterone regulate changes in CD14 and CD200R mRNA in response to
acute stressor exposure as well. Therefore, the goals of the following experiments were to
determine whether changes in multiple neuroinflammatory factors provoked by footshock (a) all
occur as a result of increased noradrenergic signaling; and (b) whether endogenous
corticosterone constrains these neuroinflammatory responses. To do this, adult male Sprague-
Dawley rats were exposed to 80 inescapable footshocks (0.8 mA, 5 sec each, 90 sec variable
inter-trial interval) over approximately 2 hr or remained in the homecage as non-stressed
controls. In Exp 1, rats were pre-treated with propranolol (20 mg/kg ip) or vehicle 15 min prior
to footshock. As predicted, propranolol blocked the hypothalamic IL-1 mRNA response.
Interestingly, propranolol also blocked the increase in CD14 mRNA, but had no effect on the
footshock-dependent suppression of CD200R mRNA. In experiment 2, rats were injected with
metyrapone (100 mg/kg sc) and aminoglutethimide (100 mg/kg sc) or equivolume vehicle, 2.5
and 1 hr respectively, prior to footshock exposure to suppress corticosterone synthesis. As
expected, blockade of corticosterone synthesis augmented the hypothalamic IL-1 mRNA
response to footshock. Interestingly, metyrapone significantly increased hypothalamic CD14
mRNA in combination with footshock exposure, but had no effect on the CD200R mRNA
downregulation. Together, these data demonstrate the induction of the neuroinflammatory factors
IL-1 and CD14 mRNA within the hypothalamus during acute stress, are driven by
norepinephrine and constrained by corticosterone.
Disclosures: P. Blandino , None; C.J. Barnum, None; B.S. Lankow, None; S. Zola, None; T.
Deak, None.
Poster
280. Stress and the Brain: Stress and Neuroimmunology I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm