Mitogen-activated protein kinase contributes to lipopolysaccharide-induced activation of corticotropin-releasing hormone synthesizing neurons in the hypothalamic paraventricular nucleus

Endocrinology
Praful S SingruRonald M Lechan

Abstract

To determine whether the p44/p42 MAPK (ERK1/2) signaling pathway is involved in the activation of CRH-containing neurons in the hypothalamic paraventricular nucleus (PVN) after bacterial lipopolysaccharide (LPS) administration, Sprague Dawley rats were injected with LPS, and studied after 2, 6, 9, and 12 h. In saline-treated controls, isolated weak phosphorylated (phospho)ERK1/2 immunoreactive neurons were observed in the PVN. However, a dramatic increase in phospho-ERK1/2 immunoreactivity was apparent in the PVN 2 h after LPS administration, and gradually declined to baseline levels 9-12 h after injection. By double-labeling immunofluorescence, all CRH-containing neurons in the PVN contained phospho-ERK1/2 2 h after LPS. Intracerebroventricular administration of the MAPK inhibitor, PD98059, prevented LPS-induced ERK1/2 phosphorylation, c-fos activation, and the increase of CRH gene expression in the PVN but had no effect on c-fos activation in brainstem A2-C1/C2 regions. We conclude that LPS rapidly increases the phospho-ERK1/2 in CRH-containing neurons in the PVN and that activation of MAPKs is necessary for LPS-induced activation of the hypothalamic-pituitary-adrenal axis.

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Citations

Dec 16, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Arshad M KhanAlan G Watts
Feb 18, 2014·Chronobiology International·Natalia PaladinoDiego A Golombek
Jun 1, 2015·Chemico-biological Interactions·Yanfei WangLai K Leung
Sep 28, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Shun-Guang WeiRobert B Felder

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