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Contrôle noradrénergique de la plasticité neurochimique et structurale dans le noyau supra-optique de l'hypothalamus chez la souris

Abstract : The magnocellular neurons of supraoptic nuclei (SON) participate in the synthesis and the release of vasopressin (AVP) and oxytocin (OT). This nucleus undergoes a reversible neurochemical and structural plasticity in response to physiological stimulations such as lactation, parturition and dehydration. Noradrenalin (NA) plays a critical role in this plasticity but the precise mechanisms of this regulation are not yet well elucidated. Indeed, many factors could be implicated in this regulation. Here we chose to study two of these factors: nitric oxide (NO) and metalloproteinases (MMP).

We used an ex-vivo model of hypothalamus slices (400µm) of C3H male mouse, containing the SON, maintained in an incubation chamber, under various pharmacological conditions. These slices underwent pharmacological treatments for 1h or 4h in the presence of NA. In order to determine the implication of NO or MMP in the NA signalling pathway;,treatments by L-arginine methyl ester (L-NAME, inhibitor of NO), sodium nitroprusside (SNP, donor of NO), the EGTA (inhibitor of Ca+2), and phenanthroline (inhibitor of MMP) were carried out. A quantification of the two peptides synthesized by magnocellular neurons under these conditions was carried out by enzymatic immuno-assay, and the study of the expression and the activity of the different peptides and factors were carried out by immunohistochemistry, histoenzymology, and in situ zymography.

In the first part of this work, we showed that NA stimulates the expression of AVP and OT validating thus our ex-vivo model. In parallel, an increase in the expression of nNOS and iNOS, and also in the activity of NADPH-diaphorase by NA was observed in the magnocellular neurons of the SON. No detection of eNOS was observed in the SON. Combining L-NAME to NA treatment, we showed that NO is implicated in the NA regulation of AVP but not that of OT. Using a blocker of the activity of nNOS we showed that NO implicated in the regulation of AVP by NA originated from nNOS and iNOS.

In the second part of this work, we showed that the neurochemical plasticity induced by NA could imply ECM molecules. We showed that MMP2 and MMP9 are expressed in vasopressin and oxytocin neurons and also in astrocytes. We then showed that NA increases the expression and the activity of these MMPs in magnocellular neurons of the SON. The implication of MMP2 and MMP9 in the regulation of the AVP and the OT by NA, realized by immunohistochemistry using an inhibitor of MMPs, demonstrated that these MMPs could be one of the factors implicated in the plasticity of the magnocellular neurons of SON.
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https://tel.archives-ouvertes.fr/tel-00167335
Contributor : Nasren Maolood <>
Submitted on : Wednesday, April 30, 2008 - 4:54:40 PM
Last modification on : Thursday, December 10, 2020 - 10:55:01 AM
Long-term archiving on: : Thursday, September 23, 2010 - 4:35:31 PM

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  • HAL Id : tel-00167335, version 3

Citation

Nasren Maolood. Contrôle noradrénergique de la plasticité neurochimique et structurale dans le noyau supra-optique de l'hypothalamus chez la souris. Neurosciences [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2007. Français. ⟨tel-00167335v3⟩

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