Matrix metalloproteinases MMP2 and MMP9 are upregulated by noradrenaline in the mouse neuroendocrine hypothalamus

Magnocellular neurons of the hypothalamic supraoptic nuclei (SON) are involved in the synthesis and release of two major neuropeptides: oxytocin (OT) and arginine-vassopressin (AVP). Neurochemical plasticity in this system is induced by physiological conditions such as lactation, parturition and dehydration, and may be accompanied by reversible structural plasticity affecting neurons, astrocytes and the extracellular matrix (ECM). The noradrenergic system plays a critical role in triggering this chemical plasticity associated with structural plasticity. Matrix metalloproteinases (MMPs) are good candidates for involvement in the ECM remodelling observed in structural plasticity. We investigated the possible regulation of the two gelatinases, MMP2 and MMP9, by noradrenaline (NA) in the mouse neuroendocrine hypothalamus. We looked for the presence, location and activity of MMP2 and MMP9 in the SON, using an ex vivo experimental model of mouse hypothalamic slices incubated for 4 h with 10(-4) m NA. We showed that: (i) immunoreactivity for MMP2 and MMP9 was detected not only in AVP-positive and OT-positive magnocellular neurons, but also in astrocyte processes in control and NA-treated slices; (ii) the number of MMP2- and MMP9-positive cells increased after incubation with NA; (iii) MMP2 and MMP9 displayed markedly higher levels of gelatinolytic activity after NA treatment. These results suggest that both MMP2 and MMP9 are regulated by NA, and could therefore also be involved in structural plasticity within the SON.