Involvement of nitric oxide in photodynamic injury of neurons and glial cells

[Display omitted] ► NO protects neurons and glial cells from necrosis induced by photodynamic treatment. ► NO enhances apoptosis of glial cells induced by photodynamic treatment. ► The proapoptotic effect of NO on glial cells could be mediated by protein kinase G. Photodynamic therapy (PDT) is a potential tool for treatment of brain tumors. However, not only malignant but also healthy neurons and glial cells may be damaged during PDT. Nitric oxide is an important modulator of cell viability and intercellular neuroglial communications. In order to study its role in photodynamic injury of normal neurons and surrounding glial cells, we used the crayfish stretch receptor that consists of only two identified sensory neurons enveloped by glial cells. Photodynamic treatment with alumophthalocyanine Photosens and diode laser (670nm, 0.4W/cm2) induced firing elimination, necrosis of neurons and glia, and apoptosis of glial cells. NO generated by exogenous generators NONOate or sodium nitroprussside protected neurons and glial cells from PDT-induced necrosis but enhanced PDT-induced apoptosis of glial cells. Application of various inhibitors of NO synthase showed that the anti-necrotic effect of NO could be related, at least in glial cells, to its production by neuronal rather than inducible isoform of this enzyme. Unlike, the pro-apoptotic effect of NO on glial cells could be, at least in part, associated with inducible NO synthase. The proapoptotic effect of NO on glial cells could be mediated by protein kinase G, which is activated by NO-dependent production of cGMP, because it inhibition reduced the PDT-induced glial apoptosis.