Jurek, Benjamin and Slattery, David A. and Maloumby, Rodrigue and Hillerer, Katharina and Koszinowski, Sophie and Neumann, Inga D. and van den Burg, Erwin H. (2012) Differential Contribution of Hypothalamic MAPK Activity to Anxiety-Like Behaviour in Virgin and Lactating Rats. PLOS ONE, 7 (5): e37060. ISSN 1932-6203,
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PARAVENTRICULAR NUCLEUS; SYNAPTIC PLASTICITY; OXYTOCIN RECEPTOR; BRAIN OXYTOCIN; KINASE; VASOPRESSIN; EXPRESSION; MEMORY; MICE; AMYGDALA; |
| Subjects: | 500 Science > 570 Life sciences 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 May 2020 05:01 |
| Last Modified: | 14 May 2020 05:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18736 |
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