Repeated stressor exposure regionally enhances beta-adrenergic receptor-mediated brain IL-1β production.
It has been proposed that increased brain cytokines during repeated stressor exposure can contribute to neuropathological changes that lead to the onset of depression. Previous studies demonstrate that norepinephrine acting via beta-adrenergic receptors (β-ARs) mediate brain IL-1 production during acute stressor exposure. The aim of the current studies was to examine how the regulation of brain cytokines by adrenergic signaling might change following repeated stressor exposure. Fischer rats were exposed to four days of chronic mild stress and 24h after the last stressors β-AR expression, norepinephrine turnover, and β-AR-mediated induction of brain IL-1 were measured in limbic areas (e.g. hypothalamus, hippocampus, amygdala, and prefrontal cortex) and brainstem. Repeated stressor exposure resulted in decreases in β-AR expression (B(max)) measured by saturation binding curves in many limbic brain areas, while an increase was observed in the brainstem. This coincided with significant increases in norepinephrine turnover in the prefrontal cortex, hypothalamus, and amygdala, a significant increase in norepinephrine turnover was not observed in the hippocampus or brainstem. Stress increased overall IL-1 production in the amygdala (both basal and stimulated). While stress did not affect basal IL-1 levels in any other brain area, central administration of isoproterenol (a β-AR agonist) augmented IL-1 production in the hypothalamus of stressed animals. These data indicate that repeated stressor exposure results in brain area specific enhancements in β-AR-mediated IL-1 production and extends current knowledge of stress-induced enhancement of brain cytokine beyond sensitized response to immunological stimuli.
Kent State University, Biological Sciences Department, Kent, OH 44242, USA.
Veronica M
VM
Porterfield
Kristin M
KM
Gabella
Mark A
MA
Simmons
John D
JD
Johnson
D000818:Animals; D001921:Brain / Q000276:immunology*; D003863:Depression / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D009638:Norepinephrine / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000276:immunology*; D013312:Stress, Physiological
D053583:Interleukin-1beta; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine