The Potential Role of Nitric Oxide Synthase in Survival and Regeneration of Magnocellular Neurons of Hypothalamo-Neurohypophyseal System

Abstract

Previous investigations from this laboratory have demonstrated that hypophysectomy induces up-regulation of neuronal nitric oxide synthase (nNOS) in magnocellular neurons of the mammalian hypothalamo-neurohypophyseal system (HNS). Accompanied by this upregulation of nNOS, both neuronal regeneration and degeneration are also observed in this system following hypophysectomy. The specific aim of this study was to determine the potential role of nNOS upregulation in neuronal survival and regeneration after hypophysectomy in the adult Sprague-Dawley (SD) rat by using a competitive nitric oxide synthase blocker, N(G)-nitrol-L: -arginine methyl ester (L: -NAME). We found that L: -NAME treatment effectively blocked the regeneration of magnocellular neurons of the rodent hypothalamus as observed in the lumen of the third cerebral ventricle following hypophysectomy. However, L: -NAME had no effect on the survival of magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei after hypophysectomy. These results suggest that the induced increase of nNOS expression enhance the regenerative ability of magnocellular neurons of the HNS following hypophysectomy.

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“…With the passage of time, magnocellular cells in the SON and PVN were gradually lost due to apoptosis, leading to insufficient AVP and OXT to maintain the normal level of urination and balance of electrolytes and fluids, a feature that is permanent in some patients [ 10 ]. However, in our study, the animals exhibited a recovery phase, or phase IV, which is likely due to neuronal and axonal regeneration in the ectopic neural lobe and to angiogenesis [ 26 , 27 , 28 , 29 , 30 ].…”