Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.

The c-Raf - MEK1/2 - ERK1/2 mitogen-activated protein kinase (MAPK) intracellular signalling cascade in neurons plays important roles in the control of a variety of behaviours, including social behaviours and anxiety. These roles partially overlap with those described for oxytocin (OXT), and it has...

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Autores principales:	Benjamin Jurek, David A Slattery, Rodrigue Maloumby, Katharina Hillerer, Sophie Koszinowski, Inga D Neumann, Erwin H van den Burg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/797347f995394f75bc2e274512759ea3
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spelling	oai:doaj.org-article:797347f995394f75bc2e274512759ea32021-11-18T07:18:21ZDifferential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.1932-620310.1371/journal.pone.0037060https://doaj.org/article/797347f995394f75bc2e274512759ea32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22615888/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The c-Raf - MEK1/2 - ERK1/2 mitogen-activated protein kinase (MAPK) intracellular signalling cascade in neurons plays important roles in the control of a variety of behaviours, including social behaviours and anxiety. These roles partially overlap with those described for oxytocin (OXT), and it has been shown that OXT activates the MAPK pathway in the hypothalamus (of male), and hippocampus (of female) rats. Here, by combining behavioural (light/dark box) and biochemical analyses (western blotting), we tested two hypotheses: (i) that OXT is anxiolytic within the hypothalamus of females, and (ii) that this effect, as well as that of lactation-associated anxiolysis, depends on the recruitment of the MAPK pathway. We found that, when injected bilaterally into the hypothalamic paraventricular nucleus (PVN), OXT decreased anxiety-like behaviour in virgins, and that this effect depended on phosphorylation of MEK1/2. MAPK pathway activation in lactation was evident by high phosphorylated (p) MEK1/2 levels, and nuclear translocation of ERK1. The high pMEK1/2 levels were necessary for the anxiolytic phenotype typically observed during lactation. Interestingly, exogenous OXT in lactating rats reduced pMEK1/2 levels without a concomitant effect on anxiety, indicating that OXT receptor activation can lead to recruitment of additional intracellular pathways to modulate MEK activity. Still other pathways could include MEK, but without subsequent activation of ERK, as we did not observe any increase in OXT-induced ERK phosphorylation. Together the results demonstrate that the MAPK pathway, especially MEK1/2, is critically involved in the regulation of anxiety-like behaviour in female rats.Benjamin JurekDavid A SlatteryRodrigue MaloumbyKatharina HillererSophie KoszinowskiInga D NeumannErwin H van den BurgPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37060 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin Jurek David A Slattery Rodrigue Maloumby Katharina Hillerer Sophie Koszinowski Inga D Neumann Erwin H van den Burg Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.
description	The c-Raf - MEK1/2 - ERK1/2 mitogen-activated protein kinase (MAPK) intracellular signalling cascade in neurons plays important roles in the control of a variety of behaviours, including social behaviours and anxiety. These roles partially overlap with those described for oxytocin (OXT), and it has been shown that OXT activates the MAPK pathway in the hypothalamus (of male), and hippocampus (of female) rats. Here, by combining behavioural (light/dark box) and biochemical analyses (western blotting), we tested two hypotheses: (i) that OXT is anxiolytic within the hypothalamus of females, and (ii) that this effect, as well as that of lactation-associated anxiolysis, depends on the recruitment of the MAPK pathway. We found that, when injected bilaterally into the hypothalamic paraventricular nucleus (PVN), OXT decreased anxiety-like behaviour in virgins, and that this effect depended on phosphorylation of MEK1/2. MAPK pathway activation in lactation was evident by high phosphorylated (p) MEK1/2 levels, and nuclear translocation of ERK1. The high pMEK1/2 levels were necessary for the anxiolytic phenotype typically observed during lactation. Interestingly, exogenous OXT in lactating rats reduced pMEK1/2 levels without a concomitant effect on anxiety, indicating that OXT receptor activation can lead to recruitment of additional intracellular pathways to modulate MEK activity. Still other pathways could include MEK, but without subsequent activation of ERK, as we did not observe any increase in OXT-induced ERK phosphorylation. Together the results demonstrate that the MAPK pathway, especially MEK1/2, is critically involved in the regulation of anxiety-like behaviour in female rats.
format	article
author	Benjamin Jurek David A Slattery Rodrigue Maloumby Katharina Hillerer Sophie Koszinowski Inga D Neumann Erwin H van den Burg
author_facet	Benjamin Jurek David A Slattery Rodrigue Maloumby Katharina Hillerer Sophie Koszinowski Inga D Neumann Erwin H van den Burg
author_sort	Benjamin Jurek
title	Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.
title_short	Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.
title_full	Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.
title_fullStr	Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.
title_full_unstemmed	Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.
title_sort	differential contribution of hypothalamic mapk activity to anxiety-like behaviour in virgin and lactating rats.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/797347f995394f75bc2e274512759ea3
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Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.

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