Extracellular signal-regulated kinase phosphorylation in forebrain neurones contributes to osmoregulatory mechanisms

Julien Dine, Vincent R. R. Ducourneau, Valérie S. Fénelon, Pascal Fossat, Aurélie Amadio, Matthias Eder, Jean-Marc Israel, Stéphane H. R. Oliet, Daniel L. Voisin
The Journal of Physiology. 2014-03-06; 592(7): 1637-1654
DOI: 10.1113/jphysiol.2013.261008

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1. J Physiol. 2014 Apr 1;592(7):1637-54. doi: 10.1113/jphysiol.2013.261008. Epub
2014 Feb 3.

Extracellular signal-regulated kinase phosphorylation in forebrain neurones
contributes to osmoregulatory mechanisms.

Dine J(1), Ducourneau VR, Fénelon VS, Fossat P, Amadio A, Eder M, Israel JM,
Oliet SH, Voisin DL.

Author information:
(1)Inserm, U862, Neurocentre Magendie, Université de Bordeaux, 146 Rue
Léo-Saignat, F-33077 Bordeaux, France. .

Vasopressin secretion from the magnocellular neurosecretory cells (MNCs) is
crucial for body fluid homeostasis. Osmotic regulation of MNC activity involves
the concerted modulation of intrinsic mechanosensitive ion channels, taurine
release from local astrocytes as well as excitatory inputs derived from
osmosensitive forebrain regions. Extracellular signal-regulated protein kinases
(ERK) are mitogen-activated protein kinases that transduce extracellular stimuli
into intracellular post-translational and transcriptional responses, leading to
changes in intrinsic neuronal properties and synaptic function. Here, we
investigated whether ERK activation (i.e. phosphorylation) plays a role in the
functioning of forebrain osmoregulatory networks. We found that within 10 min
after intraperitoneal injections of hypertonic saline (3 m, 6 m) in rats, many
phosphoERK-immunopositive neurones were observed in osmosensitive forebrain
regions, including the MNC containing supraoptic nuclei. The intensity of ERK
labelling was dose-dependent. Reciprocally, slow intragastric infusions of water
that lower osmolality reduced basal ERK phosphorylation. In the supraoptic
nucleus, ERK phosphorylation predominated in vasopressin neurones vs. oxytocin
neurones and was absent from astrocytes. Western blot experiments confirmed that
phosphoERK expression in the supraoptic nucleus was dose dependent.
Intracerebroventricular administration of the ERK phosphorylation inhibitor U
0126 before a hyperosmotic challenge reduced the number of both
phosphoERK-immunopositive neurones and Fos expressing neurones in osmosensitive
forebrain regions. Blockade of ERK phosphorylation also reduced hypertonically
induced depolarization and an increase in firing of the supraoptic MNCs recorded
in vitro. It finally reduced hypertonically induced vasopressin release in the
bloodstream. Altogether, these findings identify ERK phosphorylation as a new
element contributing to the osmoregulatory mechanisms of vasopressin release.

DOI: 10.1113/jphysiol.2013.261008
PMCID: PMC3979616
PMID: 24492838 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus