L-Deprenyl is selective and irreversible monoamine oxidase B inhibitor, known to have neuroprotective properties. Putrescine, one of polyamine, is thought to be important in the neuronal cell damage associated with various type of excitatory neurotoxicity. We examined the effects of L-deprenyl on the changes in putrescine level and neuronal damage after transient global ischemia in ger-bils. Male Mongolian gerbils weighing 65 - 75 g were used in the experiment. Global ischemia was induced by occlusion of common carotid arteries for 3 min to observe neuronal injury in hippocampal pyramidal cells. L-Deprenyl group was given 10 mg/kg of L-deprenyl intraperitoneally immediately after, 3 h and 6 h after global ischemia. Treated animals were processed in parallel with ischemic animals receiving saline as a vehicle and with sham- operated controls. Hippocampal putrescine level was increased by global ischemia and inhibited by L-deprenyl treatment. In histological findings, counts of viable neurons were made in the pyramidal cell layer of the hippocampal CA1 area 3 days after ischemic insult. The number of viable neurons in the pyramidal cell layer of CA1 area was significantly increased in animals treated with L-deprenyl compared to vehicle-treated ischemic animals (p < 0.05). In terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick endlabeling (TUNEL) assay, semiquantitative analysis of dark-brown neuronal cells was made in the hippocampal CA1 area. There was also a significant difference in the degree of TUNEL staining in the hippocampal CA1 area between vehi-cle-treated and L-deprenyl-treated animals (p < 0.05). These data show L-deprenyl is effective as a prophylactic treatment for neuronal injury when it is administrated before ischemia but a further study need to know the effects of administration of L-deprenyl after ischemia and at given times after reper-fusion.
Williams, K., Romano, C. and Molinoff, P.B. (1989) Effects of Polyamines on the Binding of [3H]-MK-801 to the NMDA Receptor: Pharmacological Evidence for the Existence of a Polyamine Recognition Site. Molecular Pharmacology, 36, 575-581.
Gilad, G.M. and Gilad, V.H. (1992) The Brain Polyamine-Stress-Response: Recurrence after Repetitive Stressor and Inhibition by Lithium. Journal of Neurochemistry, 67, 1992-1996. https://doi.org/10.1046/j.1471-4159.1996.67051992.x
Dogan, A., Rao, A.M., Hatcher, J., Rao, V.A.R., Baskaya, M.K. and Dempsey, R.J. (1999) Effects of MDL 72527, a Specific Inhibitor of Polyamine Oxidase, on Brain Edema, Ischemic Injury Volume, and Tissue Polyamine Levels in Rats after Temporary Middle Cerebral Artery Occlusion. Journal of Neurochemistry, 72, 765-770. https://doi.org/10.1046/j.1471-4159.1999.0720765.x
Paschen, W., Hallmayer, J. and Mies, G. (1987) Regional Profile of Polyamines in Reversible Cerebral Ischemia of Mongolian Gerbils. Neurochemical Pathololgy, 7, 143-156. https://doi.org/10.1007/BF02834214
Dempsey, R.J., Carney, J.M. and Kindy, M.S. (1991) Modulation of Ornithine Decarboxylase mRNA Following Transient Ischemia in the Gerbil Brain. Journal of Cerebral Blood Flow and Metabolism, 11, 979-985. https://doi.org/10.1038/jcbfm.1991.164
Kindy, M.S., Hu, Y. and Dempsey, R.J. (1994) Blockade of Ornithine Decarboxylase Enzyme Protects against Ischemic Brain Damage. Journal of Cerebral Blood Flow and Metabolism, 14, 1040-1045. https://doi.org/10.1038/jcbfm.1994.136
Philips, S.R. and Boulton, A.A. (1979) The Effect of Monoamine Oxidase on Some Srylalbylamines in Rat Striatum. Journal of Neurochemistry, 33, 159-167. https://doi.org/10.1111/j.1471-4159.1979.tb11718.x
Carrillo, M.C., Kitani, K., Kanai, S., Sato, Y. and Ivy, G.O. (1992) The Ability of (-) Deprenyl to Increase Superoxide Dismutase Activities in the Rat Is Tissue and Brain Region Selective. Life Science, 50, 1985-1992.
Loscher, W. and Lehmann, H. (1996) L-Deprenyl (Selegiline) Exerts Anticonvulsant Effects against Different Seizure Types in Mice. The Journal of Pharmacology and Experimental Therapeutics, 277, 1410-1417.
Matsushita, K., Kitagawa, K., Matsuyama, T., Ohtsuki, T., Taguchi, A., Mandai, K., Mabuchi, T., Yagita, Y., Yanagihara, T. and Matsumoto, M. (1996) Effect of Systemiczinc Administration on Delayed Neuronal Death in the Gerbil Hippocampus. Brain Research, 743, 362-365.
Iqbal, Z. and Koenig, H. (1985) Polyamines Appear to Be Second Messengers in Mediating Ca++ Fluxes and Neuro-transmitter Release Potassium-Depolarized Synaptosomes. Biochemical and Biophysical Research Communications, 133, 563-573. https://doi.org/10.1038/305530a0
Najm, I., el-Skaf, G., Massicotte, G., Vanderklish, P., Lynch, G. and Baudry, M. (1992) Changes in Polyamine Levels and Spectrin Degradation Following Kainate-Induced Seizure Activity: Effect of Difluoromethylornithine. Experimental Neurology, 116, 345-354. https://doi.org/10.1111/j.1471-4159.1991.tb02091.x
De Vera, N., Artigas, F., Serratosa, J. and Martinez, E. (1991) Changes in Polyamine Levels in Rat Brain after Systemic Kainic Acid Administration: Relationship to Convulsant Activity and Brain Damage. Journal of Neurochemistry, 57, 1-8.
Zoli, M., Pedrazzi, P., Zini, I. and Agnati, L.F. (1996) Spermidine/Spermine N1-Acetyltransferase mRNA Levels Show Marked and Region-Specific Changes in the Early Phase after Transient Forebrain Ischemia. Molecular Brain Research, 38, 122-134.
Rao, A.M., Hatcher, J.F., Baskaya, M.K. and Dempsey, R.J. (1998) Simultaneous Assay of Ornithine Decarboxylase and Polyamines after Central Nervous System Injury in Gerbil and Rat. Neuroscience Letters, 256, 65-68. https://doi.org/10.1111/j.1471-4159.1988.tb01818.x
Ransom, R.W. and Stec, N.L. (1988) Cooperative Modulation of [3H] MK-801 Binding to the NMDA Receptor-Ion Channel Complex by l-Glutamate, Glycine, and Polyamines. Journal of Neurochemistry, 51, 830-836. https://doi.org/10.1007/s12192-010-0177-y
Subramanian, M.V. and James, T.J. (2010) Age-Related Protective Effect of Deprenyl on Changes in the Levels of Diagnostic Marker Enzymes and Antioxidant Defense Enzymes Activities in Cerebellar Tissue in Wistar Rats. Cell Stress Chaperones, 15, 743-751. https://doi.org/10.1111/j.1749-6632.1996.tb39078.x
Wu, R.M., Murphy, D.L. and Chiueh, C.C. (1996) Suppression of Hydroxyl Radical Formation and Protection of Nigral Neurons by l-Deprenyl (Selegiline). Annals of the New York Academy of Sciences, 15, 379-390.
Tsunekawa, H., Noda, Y., Mouri, A., Yoneda, F. and Nabeshima, T. (2008) Synergistic Effects of Selegiline and Donepezil on Cognitive Impairment Induced by Amyloid Beta (25-35). Behavioral Brain Research, 190, 224-232. https://doi.org/10.1074/jbc.M505843200
Hetz, C., Vitte, P.A., Bombrun, A., Rostovtseva, T.K., Montessuit, S., Hiver, A., Schwarz, M.K., Church, D.J., Korsmeyer, S.J., Martinou, J.C. and Antonsson, B. (2005) Bax Channel Inhibitors Prevent Mitochondrion-Mediated Apoptosis and Protect Neurons in a Model of Global Brain Ischemia. Journal of Biological Chemistry, 280, 42960-42970. https://doi.org/10.1007/BF00294608
Yamamoto, K., Hayakawa, T., Mogami, H., Akai, F. and Yanagihara, T. (1990) Ultrastructural Investigation of the CA1 Region of the Hippocampus after Transientcerebral Ischemia in Gerbil. Acta Neuropathologica, 80, 487-492.
Chan, P.H., Kawase, M., Murakami, K., Chen, S.F., Li, Y., Calagui, B., Reola, L., Carlson, E. and Epstein, C.J. (1998) Overexpression of SOD1 in Transgenic Rats Protects Vulnerable Neurons against Ischemic Damage after Global Cerebral Ischemia and Reperfusion. Journal of Neuroscience, 18, 8292-8299. https://doi.org/10.1161/01.STR.30.9.1962
Kawase, M., Murakami, K., Fujimura, M., Morita-Fujimura, Y., Gasche, Y., Kondo, T., Scott, R.W. and Chan, P.H. (1999) Exacerbation of Delayed Cell Injury after Transient Global Ischemia in Mutant Mice with CuZn Superoxide Dismutase Deficiency. Stroke, 30, 1962-1968.