Oxytocin alters the morphology of hypothalamic neurons via the transcription factor myocyte enhancer factor 2A (MEF-2A)

In this study, we present evidence for three hypotheses: 1) OT leads to neurite retraction in hypothalamic neurons via the OT receptor (OTR) 2) The transcription factor MEF-2A is a central regulator of OT-induced neurite retraction, and 3) The MAPK pathway is critical for OT-induced MEF-2A activation.Incubation of rat hypothalamic H32 cells with 10 nM to 1 μM OT, vasopressin, and the specific OTR agonist TGOT, over the course of 12 h resulted in a time-dependent, significant retraction of neurites. In addition, the size of the nuclear compartment increased, whereas the overall cell size remained unchanged. OT treatment for 10 h increased the cellular viability significantly, and this effect could be blocked by a specific OTR antagonist, providing evidence for a specific and pro-active effect of OT on neurite retraction, and not as an unspecific side effect of apoptosis.The molecular mechanism that controls OT-induced neurite retraction includes a reduced phosphorylation of the transcription factor MEF-2A at Serine 408 (S408). This dephosphorylation is under the control of the OTR-coupled MAPK pathway, as blocking MEK1/2 by U0126 inhibited MEF-2A activation and subsequent neurite retraction. The siRNA-mediated knockdown of MEF-2A prevented the OT-induced neurite retraction, providing direct evidence for a role of MEF-2A in morphological alterations induced by OT treatment.In summary, the present study reveals a previously unknown OTR-coupled MAPK-MEF-2A pathway, whi...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research