Protection of Crayfish Glial Cells but not Neurons from Photodynamic Injury by Nerve Growth Factor

Abstract

Photodynamic treatment that causes intense oxidative stress and cell death is currently used in neurooncology. However, along with tumor cells, it may damage healthy neurons and glia. In order to study photodynamic effect on normal nerve and glial cells, we used crayfish stretch receptor, a simple system consisting of only two identified sensory neurons surrounded by glial cells. Photodynamic treatment induced firing abolition and necrosis of neurons as well as necrosis and apoptosis of glial cells. Nerve growth factor but not brain-derived neurotrophic factor or epidermal growth factor protected glial cells but not neurons from photoinduced necrosis and apoptosis. Inhibitors of tyrosine kinases or protein kinase JNK eliminated anti-apoptotic effect of nerve growth factor in photosensitized glial cells but not neurons. Therefore, these signaling proteins were involved in the anti-apoptotic activity of nerve growth factor. These data indicate the possible presence of receptors capable of recognizing murine nerve growth factor in crayfish glial cells. Thus, intercellular signaling mediated by nerve-growth-factor-like neurotrophin, receptor tyrosine kinase, and JNK may be involved in crayfish glia protection from apoptosis induced by photodynamic treatment.

On the Role of Phosphatidylinositol 3-Kinase, Protein Kinase B/Akt, and Glycogen Synthase Kinase-3β in Photodynamic Injury of Crayfish Neurons and Glial Cells

“…Apoptotic nuclear fragmentation was never observed in photosensitized neurons but some glial nuclei got fragmented after PDT (Fig. 1c, d) as described earlier (Uzdensky et al 2002(Uzdensky et al , 2005Lobanov and Uzdensky 2009). The level of glial apoptosis significantly increased after PDT (Figs.…”

“…The protective, anti-apoptotic effect of this neuron could be mediated by the release of some neurotrophic factors that initiate anti-apoptotic signaling processes in the surrounding glial cells. Actually, the application of nerve growth factor (NGF) protected glial cells but not neurons from PDTinduced necrosis and apoptosis (Lobanov and Uzdensky 2009). Neurotrophins are recognized by receptor tyrosine kinases that may initiate Ca 2+ -, MAP kinase-, and phosphatidylinositol 3-kinase-related signaling pathways, which regulate cell survival (Sofroniew et al 2001).…”

“…Neurotrophins are recognized by receptor tyrosine kinases that may initiate Ca 2+ -, MAP kinase-, and phosphatidylinositol 3-kinase-related signaling pathways, which regulate cell survival (Sofroniew et al 2001). The role of the first two pathways in PDT-induced death of crayfish neurons and glial cells has been studied earlier (Lobanov and Uzdensky 2009;Uzdensky et al 2005Uzdensky et al , 2007, but the role of the third pathway remained unclear.…”

Photodynamic therapy: a review of applications in neurooncology and neuropathology

“…In fact, neurotrophic factors, nerve growth factor (NGF), and glia-derived growth factor but not brain-derived growth factor or ciliary neurotrophic factor protected glial cells (but not neurons) from PDT-induced necrosis and apoptosis. 80,81 NGF-mediated protection of glial cells from PDT-induced apoptosis was mediated by mitogen-activated protein kinase JNK. 80 Unlike another mitogen-activated protein, kinase p38 was involved in PDT-induced glial necrosis but not apoptosis.…”

“…80,81 NGF-mediated protection of glial cells from PDT-induced apoptosis was mediated by mitogen-activated protein kinase JNK. 80 Unlike another mitogen-activated protein, kinase p38 was involved in PDT-induced glial necrosis but not apoptosis. Nitric oxide (NO), another intercellular messenger, could also influence PDT-induced death of neurons and glia.…”