Nitric Oxide Synthase (NOS) Isoform Expression after Peripheral Nerve Transection in Mice

Abstract

Localization of the nitric oxide (NO)-producing enzyme, nitric oxide synthase (NOS), and its functions are currently being investigated in several tissues and organs. It has been suggested that NO is involved in nerve cell death and the development of neurodegenerative disease. The purpose of this study was to immunohistochemically investigate expression of NOS to clarify its function in the degeneration and regeneration of transected mouse sciatic nerve. Scattered neuronal NOS (nNOS)-positive Schwann cells observed on the central side of the stump on day 1 after transection showed an increase in number on day 7. None were observed at the stump on day 14, however. Expression of nNOS was observed in axons extending from the stump. The number of nNOS-positive axons increased on day 21. Inducible NOS was expressed in inflammatory cells at the stump on day 1. This positive reaction subsequently weakened by day 7, however. Endothelial NOS was expressed in blood vessels at the stump on day 7, but decreased thereafter. The results of the present study suggest that NO is involved in the proliferation and migration of Schwann cells, as well as in axon regeneration at an early stage following nerve transection.

Regulation of iNOS on Immune Cells and Its Role in Diseases

“…Recent studies have found that NO produced by upregulated iNOS after mDC activation controls the balance of effector DCs and regulatory DCs, which is accomplished by inhibiting NF-κB signaling and inflammatory body activity [42,43,44]. We found that although the number of CD11c + CD11b + effector DCs producing IL-12, TNF-α, and IL-6 in iNOS ‒/‒ mice to be increased, the percentage of CD11c + CD11b + regulatory DCs expressing IL-10 and PD-1 was the same as that of wild type mice.…”

Heme Oxygenase 1 in Schwann Cells Regulates Peripheral Nerve Degeneration Against Oxidative Stress

“…These inhibitory effects of three drugs mean that HOs activation regulates oxidative stress during Wallerian degeneration. Interestingly, NOS2 protein expression was not found in the Western blot analysis (data not shown) because NOS2 is not present in sciatic nerves (Kikuchi et al., 2018). These three drugs also inhibited HO2 on 3DIV because CrMP, SnMP, and SnPP by competing with heme for binding HOs suppress both HO1 and HO2 (Figure 5(c)).…”