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.
References
[1]
Pegg, A.E. (1986) Recent Advances in the Biochemistry of Polyamines in Eukaryotes. Biochemical Journal, 234, 249-262. https://doi.org/10.1042/bj2340249
[2]
Tabor, C.W. and Tabor, H. (1984) Polyamines. Annual Review of Biochemistry, 53, 749-790. https://doi.org/10.1146/annurev.bi.53.070184.003533
[3]
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.
[4]
Baskaya, M.K., Rao, A.M., Prasad, M.R. and Dempsey, R.J. (1996) Regional Activity of Ornithine Decarboxylase and Edema Formation after Traumatic Brain Injury. Neurosurgery, 38, 140-145. https://doi.org/10.1097/00006123-199601000-00033
[5]
Baskaya, M.K., Rao, A.M., Puckett, L., Prasad, M.R. and Dempsey, R.J. (1996) Effect of Difluoro-Methylornithine Treatment on Regional Ornithine Decarboxylase Activity and Edema Formation after Experimental Brain Injury. Journal of Neurotrauma, 13, 85-92. https://doi.org/10.1089/neu.1996.13.85
[6]
Baskaya, M.K., Rao, A.M., Dogan, A., Donaldson, D., Gellin, G. and Dempsey, R.J. (1997) Regional Brain Polyamine Levels in Permanent Focal Cerebral Ischemia. Brain Research, 744, 302-308.
[7]
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
[8]
Gilad, G.M. and Gilad, V.H. (1992) Polyamines in Neurotrauma Ubiquitous Molecules in Search of a Function. Biochemical Pharmacology, 44, 401-407.
[9]
Lee, Y.K., Lee, S.R. and Kim, C.Y. (2000) Melatonin Attenuates the Changes in Polyamine Levels Induced by Systemic Kainate Administration in Rat Brains. Journal of Neurological Science, 178, 124-131.
[10]
Martinez, E., de Vera, N. and Artigas, F. (1991) Differential Response of Rat Brain Polyamines to Convulsant Agents. Life Science, 48, 77-84.
[11]
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
[12]
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
[13]
Paschen, W., Schmidt-Kastner, R., Hallmayer, J. and Djuricic, B. (1988) Polyamines in Cerebral Ischemia. Neurochemical Pathololgy, 9, 1-20.
[14]
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
[15]
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
[16]
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
[17]
Knoll, J. (1993) The Pharmacological Basis of the Beneficial Effects of (-) Deprenyl (Selegiline) in Parkinson’s and Alzheimer’s Disease. Journal of Neural Transmission. Supplementum, 40, 69-91.
[18]
Tetrude, J.W. and Langstone, J.W. (1989) The Effect of Deprenyl (Selegiline) on the Natural History of Parkinson’s Disease. Science, 245, 519-522. https://doi.org/10.1126/science.2502843
[19]
Knoll, J. (1978) The Possible Mechanisms of Action of (-) Deprenyl in Parkinson’s Disease. Journal of Neural Transmission, 43, 177-198. https://doi.org/10.1007/BF01246955
[20]
Kabins, D. and Gershon, S. (1990) Potential Applications for Monoamine Oxidase B Inhibitors. Dementia, 1, 323-348.
[21]
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.
[22]
Maia, F.D., Pitombeira, B.S., Araujo, D.T., Cunha, G.M. and Viana, G.S. (2004) L-Deprenyl Prevents Lipid Peroxidation and Memory Deficits Produced by Cerebral Ischemia in Rats. Cellular and Molecular Neurobiology, 24, 87-100. https://doi.org/10.1023/B:CEMN.0000012727.59502.c5
[23]
Cooper, J. (1991) Drug Treatment of Alzheimer’s Disease. Archives of Internal Medicine, 151, 245-249. https://doi.org/10.1001/archinte.1991.00400020021006
[24]
Davis, K.L. and Haroutunian, V. (1993) Strategies for the Treatment of Alzheimer’s Disease. Neurology, 43, 52-55.
[25]
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.
[26]
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.
[27]
Bondy, S.C. and Walker, C.H. (1986) Polyamine Contribute to Calcium-Stimulated Release of Aspartate from Brain Particulate Fractions. Brain Research, 371, 96-100.
[28]
Trout, J.J., Koenig, H., Goldstone, A.D. and Lu, C.Y. (1986) Blood Brain Barrier Breakdown by Cold Injury. Polyamine Signals Mediate Acute Stimulation of Endocytosis, Vesicular Transport, and Microvillus Formation in Rat Cerebral Capillaries. Laboratory Investigation, 55, 622-631.
[29]
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
[30]
Koenig, H., Goldsteine, A.D. and Lu, Ch.-Y. (1983) Polyamines Regulate Calcium Fluxes in a Rapid Plasma Membrane Response. Nature, 305, 530-534. https://doi.org/10.1146/annurev.ne.13.030190.001131
[31]
Choi, D.W. and Rothman, S.M. (1990) The Role of Glutamate Neurotoxicity in Hypoxia-Ischemic Neuronal Death. Annual Review of Neu-roscience, 13, 171-182.
[32]
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
[33]
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.
[34]
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.
[35]
Baudry, M. and Najm, I. (1997) Kainate-Induced Seizure Activity Stimulates the Polyamine Interconversion Pathway in Rat Brain. Neuroscience Letters, 171, 151-154.
[36]
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
[37]
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
[38]
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
[39]
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.
[40]
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
[41]
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
[42]
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.
[43]
Whaley, J.G., Tharakan, B., Smith, B., Hunter, F.A. and Childs, E.W. (2009) (-)-Deprenyl Inhibits Thermal Injury-Induced Apoptotic Signaling and Hyperpermeability in Microvascular Endothelial Cells. Journal of Burn Care & Research, 30, 1018-1027.
[44]
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
[45]
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.
[46]
Block, F., Schmitt, W. and Schwarz, M. (1995) The Antioxidant LY 231617 Ameliorates Functional and Morphological Sequelae Induced by Global Ischemia in Rats. Brain Research, 694, 308-311.
[47]
O’Neill, M.J., Hicks. C., Ward. M. and Panetta, .JA. (1997) Neuroprotective Effects of the Antioxidant LY231617 and NO Synthase Inhibitors in Global Cerebral Ischemia. Brain Research, 760, 170-178.
