Late Pregnancy is a Critical Period for Changes in Phosphorylated Mitogen‐Activated Protein Kinase/Extracellular Signal‐Regulated Kinase 1/2 in Oxytocin Neurones

Abstract

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The physiological demands of parturition and lactation lead to the increased pulsatile release of oxytocin (OT) into the circulation from the neurohypophysial axons of OT neurones in the supraoptic (SON) and paraventricular (PVN) nuclei. These states of increased OT release are accompanied by a significant plasticity in magnocellular OT neurones and their synaptic connections, and many of these changes require activation of a central OT receptor. The mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) is assumed to be up-regulated in the PVN during lactation, and many of the effects of OT in peripheral and brain tissue are mediated through a MAPK/ERK pathway. The present study investigated whether this pathway is altered in the SON and PVN during late pregnancy [embryonic day (E)20-21], which is a critical period for OT plasticity induction, and for lactation, when plastic changes are sustained. Based on immunoreactivity for phosphorylated ERK1/2 (pERK1/2), the results suggest an enhanced activation of MAPK/ERK pathway in OT neurones specifically during late pregnancy in both the SON and PVN. Although immunoblots from the SON confirm this pregnancy-associated up-regulation in late pregnancy, they also suggest enhancement into lactation as well. Together, the results suggest an important role for the MAPK/ERK pathway during reproductive changes in the SON and PVN.

Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy

“…The majority of our results suggested that changes in the sensitivity to TBB are most pronounced in late pregnancy. This corresponds with previous data on synaptic and neuroglial plasticity in the SON (see Armstrong 2015;Hatton 2002;Theodosis et al 2008, for reviews) as well as our recent findings of a pronounced upregulation of ERK1/2 in OT neurons at late pregnancy (Chandaka et al 2016). We thus compared blots from SON lysates from virgin and late (E20 -21) pregnant rats for three PP2A subunits (A, B and C), two CK2 subunits (CK2␣ and CK2␤), and SK3.…”

“…In addition to the antibodies listed above for Western blots, we also used an antibody to CaM (AbCam, Cambridge, MA, no. ab45689) as an additional positive control, since CaM is known to be the Ca 2ϩ sensor for SK3 channels, and an antibody to ERK1/2 (Cell Signaling Technology; see Chandaka et al 2016), which should not be associated with SK3, and finally we ran the SK3 antibody once again to verify SK3 presence in the pulldown lysates. An additional lane was run using human embryonic kidney cell lysates or an SON lysate from one of the animals.…”

Intracellular Pathways Associated with the Etiology of Autism

“…Data also suggest an enhanced activation of the MAPK/ERK pathway in OXT neurons, specifically during late pregnancy in both the SON and PVN [32].…”

Coxsackieviruses B3 infection of myocardial microvascular endothelial cells activates fractalkine via the ERK1/2 signaling pathway

“…MAPKs ERK1/2, p38, and JNK play significant roles in regulating the synthesis of inflammatory mediators such as NF-κB and activator protein-1. Conversely, the production of inflammatory mediators is completely blocked by the suppression of multiple MAPK family members ( 16 , 27 ). In this study, the total ERK1/2 protein level was increased.…”

“…The mitogen-activated protein kinase (MAPK) signaling pathway links extracellular signals with intracellular targets to control fundamental cellular processes such as proliferation, growth, migration, differentiation, embryogenesis, and death ( 15 ). MAPKs consist of three subfamilies, whose members include extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK) ( 16 ). The significance of MAPK in myocarditis has been highlighted in several reviews.…”