Abstract
Neurons and glial cells can protect each other from stress and following death by mutual exchange with neurotrophins. In order to examine involvement of different neurotrophic factors in neuroglial interactions in a photosensitized crayfish stretch receptor, a simple model object consisting of only two sensory neurons enveloped by glial cells, we studied the influence of glial cell line-derived neurotrophic factor (GDNF), neurturin, and ciliary neurotrophic factor (CNTF) on its photodynamic injury. Photodynamic treatment, which causes strong oxidative stress, induced firing abolition and necrosis of neurons, necrosis, and apoptosis of glial cells. GDNF significantly reduced photoinduced neuronal necrosis and neurturin but not CNTF showed a similar tendency. Both of them significantly reduced necrosis and apoptosis of glial cells. At the ultrastructural level, neurons and glial cells treated with GDNF in the darkness contained large mitochondria with well-developed cristae, numerous ribosomes, polysomes, rough endoplasmic reticulum (ER), and dictyosomes. This indicated the high level of bioenergetic, biosynthetic, and transport processes. Photodynamic treatment caused swelling and vacuolization of mitochondria, dictyosomes, and ER. It also impaired formation of glial protrusions and double membrane vesicles that transfer glial material into the neuron. GDNF prevented photoinduced mitochondria swelling that disturbed the cellular bioenergetics and cytoplasm vacuolization associated with injury of intracellular organelles. It also preserved the structures involved in protein synthesis and transport: rough ER, dictyosomes, polysomes, microtubule bundles, submembrane cisterns, and double membrane vesicles. GDNF-mediated maintenance of metabolism and ultrastructure of photosensitized neurons and glial cells may be the basis of its neuro- and glia protective effects.
Similar content being viewed by others
References
Airaksinen MS, Saarma M (2002) The GDNF family: signaling, biological functions and therapeutical value. Nat Rev Neurosci 3:383–394
Airaksinen MS, Holm L, Hatinen T (2006) Evolution of the GDNF family ligands and receptors. Brain Behav Evol 68:181–190
Almeida RD, Manada BJ, Carvalho AP, Duarte CB (2004) Intracellular signaling mechanisms in photodynamic therapy. Biochim Biophys Acta 1704:59–86
Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10:S18–S25
Barde YA (1994) Neurotrophic factors: an evolutionary perspective. J Neurobiol 25:1329–1333
Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Fact 22:123–131
Brown SB, Brown EA, Walker I (2004) The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol 5:497–508
Buytaert E, Dewaele M, Agostinis P (2007) Molecular pathways in cell death following photodynamic therapy. In: Uzdensky AB (ed). Photodynamic therapy at the cellular level Trivandrum: Research Signpost. p 63-96
Castano AP, Demidova TN, Hamblin MR (2005) Mechanisms in photodynamic therapy: part two—cellular signaling, cell metabolism and modes of cell death. Photodiagn Photodyn Ther 2:1–23
Chao MV, Rajagopal R, Lee FS (2006) Neurotrophin signaling in health and disease. Clin Sci (Lond) 110:167–173
Cheng H, Fu YS (2004) Ability of GDNF to diminish free radical production leads to protection against kainate-induced excitotoxicity in hippocampus. Hippocampus 14:77–86
Du Y, Dreyfus CF (2002) Oligodendrocytes as providers of growth factors. J Neurosci Res 68:647–654
Eljamel MS (2004) Brain PDD and PDT unlocking the mystery of malignant gliomas. Photodiagn Photodyn Ther 1:303–310
Fedorenko GM, Uzdensky AB (2008) Dynamics of ultrastructural changes in the isolated crayfish mechanoreceptor neuron under photodynamic impact. J Neurosci Res 86:1409–1416
Fedorenko GM, Uzdensky AB (2009a) Ultrastructure of neuroglial contacts in crayfish stretch receptor. Cell Tissue Res 337:477–490
Fedorenko GM, Uzdensky AB (2009b) Cellular structures involved in the transport processes and neuroglial interactions in the crayfish stretch receptor. J Integr Neurosci 8:433–440
Fedorenko GM, Fedorenko YP, Fedorenko AG, Uzdensky AB (2011) Dynamics of ultrastructural alterations in photosensitized crayfish glial and neuronal cells: structures involved in transport processes and neuroglial interactions. J Neurosci Res 89:341–351
Florey E, Florey E (1955) Microanatomy of the abdominal stretch receptors of the crayfish (Astacus fluviatili L.). J Gen Physiol 39:69–85
Girotti A (2001) Photosensitized oxidation of membrane lipids: reaction pathways, cytotoxic effects, and cytoprotective mechanisms. J Photochem Photobiol B: Biol 63:103–113
Hauck SM, Kinkl N, Deeg CA, Swiatek DE, Lange M, Schoffmann S, Ueffing M (2006) GDNF family ligands trigger indirect neuroprotective signaling in retinal glial cells. Mol Cell Biol 26:2746–2757
Jarro H, Fainzilber M (2006) Building complex brains—missing pieces in an evolutionary puzzle. Brain Behav Evol 68:191–195
Jarro H, Beck G, Conticello SG, Fainzilber M (2001) Evolving better brains: a need for neurotrophins? TiNS 24:79–85
Kolosov M, Uzdensky A (2006) Crayfish mechanoreceptor neuron prevents photoinduced apoptosis of satellite glial cells. Brain Res Bull 69:495–500
Kopp DM, Trachtenberg JT, Thompson WJ (1997) Glial growth factor rescues Schwann cells of mechanoreceptors from denervation-induced apoptosis. J Neurosci 17:6697–6706
Kostron H (2010) Photodynamic diagnosis and therapy and the brain. In: Gomer CJ (ed) Phorodynamic therapy. Methods and protocols. Methods in molecular biology, vol 635. Springer, New York, pp 261–280
Lobanov AV, Uzdensky AB (2009) Protection of crayfish glial cells but not neurons from photodynamic injury by nerve growth factor. J Mol Neurosci 39:308–319
McKay S, Purcell AL, Carew TJ (1999) Regulation of synaptic function by neurotrophic factors in vertebrates and invertebrates: implications for development and learning. Learn Mem 6:193–215
Messer CJ, Son JH, Joh TH, Beck KD, Nestler EJ (1999) Regulation of tyrosine hydroxylase gene transcription in ventral midbrain by glial cell line-derived neurotrophic factor. Synapse 34:241–243
Nakamura TY, Jeromin A, Smith G, Kurushima H, Koga H, Nakabeppu Y, Wakabayashi S, Nabekura J (2006) Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons. J Cell Biol 172:1081–1091
Nicole O, Ali C, Docagne F, Plawinski L, MacKenzie ET, Vivien D, Buisson A (2001) Neuroprotection mediated by glial cell line-derived neurotrophic factor: involvement of a reduction of NMDA-induced calcium influx by the mitogen-activated protein kinase pathway. J Neurosci 21:3024–3033
Odinak MM, Tsigan NV (2005) Neurotrophic growth factors in the central nervous system. Nauka, Sankt-Petersburg
Onyango IG, Tuttle JB, Bennett JP (2005) Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death. Neurobiol Dis 20:141–154
Pellitteri R, Russo A, Stanzani S (2006) Schwann cell: a source of neurotrophic activity on cortical glutamatergic neurons in culture. Brain Res 1069:139–144
Rubin GM, Yandell MD, Wortman JR et al (2000) Comparative genomics of the eukaryotes. Science 287:2204–2215
Saarma M, Sariola H (1999) Other neurotrophic factors: glial cell line-derived neurotrophic factor (GDNF). Microsc Res Tech 45:292–302
Saavedra A, Baltazar G, Carvalho CM, Duarte EP (2005) GDNF modulates HO-1 expression in substantia nigra postnatal cell cultures. Free Rad Biol Med 39:1611–1619
Saavedra A, Baltazar G, Santos P, Carvalho CM, Duarte EP (2006) Selective injury to dopaminergic neurons up-regulates GDNF in substantia nigra postnatal cell cultures: role of neuron–glia crosstalk. Neurobiol Dis 23:533–542
Sofroniew MV, Howe CL, Mobley WC (2001) Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 24:1217–1281
Stylli SS, Kaye AH (2006) Photodynamic therapy of cerebral glioma—a review. Part I. A biological basis. J Clin Neurosci 13:615–625
Ugarte SD, Lin E, Klann E, Zigmond MJ, Perez RG (2003) Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line: modulation by inhibitors of PI3 kinase and MEK. J Neurosci Res 73:105–112
Uzdensky AB (2008) Signal transduction and photodynamic therapy. Curr Sign Transduct Ther 3:55–74
Uzdensky AB (2010) Cellular and molecular mechanisms of photodynamic therapy. Nauka, Sankt-Petersburg
Uzdensky AB, Bragin DE, Kolosov MS, Dergacheva OY, Fedorenko GM, Zhavoronkova AA (2002) Photodynamic inactivation of isolated crayfish mechanoreceptor neuron: different death modes under different photosensitizer concentrations. Photochem Photobiol 76:431–437
Uzdensky A, Kolosov M, Bragin D, Dergacheva O, Vanzha O, Oparina L (2005) Involvement of adenylate cyclase and tyrosine kinase signaling pathways in response of crayfish stretch receptor neuron and satellite glia cell to photodynamic treatment. Glia 49:339–348
Venter JC, Adams MD, Myers EW et al (2001) The sequence of human genome. Science 291:1304–1351
Zigmond MJ (2006) Triggering endogenous neuroprotective mechanisms in Parkinson's disease: studies with a cellular model. J Neural Transm Suppl 70:439–442
Acknowledgments
The work was supported by grants from the Ministry of Education and Science of Russian Federation (grants 2.1.1/6185 and 1.16.11) and the Russian Foundation for Basic Research (grants 08-04-01322 and 11-04-01476).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Uzdensky, A., Komandirov, M., Fedorenko, G. et al. Protection Effect of GDNF and Neurturin on Photosensitized Crayfish Neurons and Glial Cells. J Mol Neurosci 49, 480–490 (2013). https://doi.org/10.1007/s12031-012-9858-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-012-9858-6