Noradrenaline acting at central ?-adrenoceptors induces interleukin-10 and suppressor of cytokine signaling-3 expression in rat brain: Implications for neurodegeneration

McNameea, Eon N.; Ryana, Karen M.; Griffin, Éadaoin W.; González Reyes, Rodrigo Esteban; Ryana, Katie J.; Harkin, Andrew; Connor, Thomas J.

doi:https://doi.org/10.1016/j.bbi.2010.02.005

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Noradrenaline acting at central ?-adrenoceptors induces interleukin-10 and suppressor of cytokine signaling-3 expression in rat brain: Implications for neurodegeneration

https://repository.urosario.edu.co/handle/10336/25919
https://doi.org/10.1016/j.bbi.2010.02.005

Autores

McNameea, Eon N.

Ryana, Karen M.

Griffin, Éadaoin W.

González Reyes, Rodrigo Esteban

Ryana, Katie J.

Harkin, Andrew

Connor, Thomas J.

Fecha

2010-05-01

Editor

Elsevier

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Abstract

Evidence indicates that the monoamine neurotransmitter noradrenaline elicits anti-inflammatory actions in the central nervous system (CNS), and consequently may play a neuroprotective role where inflammatory events contribute to CNS pathology. Here we examined the ability of pharmacologically enhancing central noradrenergic tone to induce expression of anti-inflammatory cytokines in rat brain. Administration of the noradrenaline reuptake inhibitor reboxetine (15 mg/kg; ip) combined with the ?2-adrenoceptor antagonist idazoxan (1 mg/kg; ip) induced interleukin-10 (IL-10) expression in rat cortex and hippocampus. In addition, these drug treatments induced IL-10 signaling as indicated by increased STAT3 phosphorylation and suppressor of cytokine signaling-3 (SOCS-3) mRNA expression. In contrast to the profound increase in IL-10 induced by the reboxetine/idazoxan combination, the other two broad spectrum anti-inflammatory cytokines IL-4 and TGF-? were not induced by this treatment. The ability of combined treatment with reboxetine and idazoxan to induce IL-10 and SOCS3 expression was mediated by ?-adrenoceptor activation, as their induction was blocked by pre-treatment with the ?-adrenoceptor antagonist propranolol. Moreover, administration of the brain penetrant ?2-adrenoceptor agonist clenbuterol induced a time- and dose-dependent increase in central IL-10 and SOCS3 expression, and the ability of clenbuterol to induce IL-10 and SOCS-3 expression was blocked by the centrally acting ?-adrenoceptor antagonist, propranolol, and was mimicked by the highly selective ?2-adrenoceptor agonist formoterol. In all, these data indicate that increasing central noradrenergic tone induces IL-10 production and signaling in the CNS, which may protect against neurodegeneration.