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Glutamate-induced cell death and formation of radicals can be reduced by lisuride in mesencephalic primary cell culture

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Summary.

Oxidative stress evoked by excitotoxicity is considered an important factor for the loss of dopaminergic neurons in Parkinson’s disease. In vitro, protective effects of the dopamine agonist lisuride on complex I inhibition in primary dopaminergic cell culture have been reported. However, little is known about the effects of lisuride on glutamate-induced radical formation. Here, effects of lisuride on the formation of nitric oxide (NO) and superoxide radicals following glutamate exposure were studied on primary cell cultures prepared from mouse mesencephala. Glutamate treatment resulted in doubling of NO and superoxide radical formation, increased dopaminergic cell degeneration and extensively altered neuronal appearance. Pretreatment with lisuride significantly lowered the levels of either reactive species and increased the survival of dopaminergic neurons compared to glutamate-treated cultures. Moreover, the beneficial effect of lisuride could be completely inhibited by the D2/D3 receptor antagonist sulpiride when co-treated in cultures.

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References

  • A Atlante P Calissano A Bobba S Giannattasio E Marra S Passarella (2001) ArticleTitleGlutamate neurotoxicity, oxidative stress and mitochondria FEBS Lett 497 1–5 Occurrence Handle11376653 Occurrence Handle1:CAS:528:DC%2BD3MXjslentrk%3D Occurrence Handle10.1016/S0014-5793(01)02437-1

    Article  PubMed  CAS  Google Scholar 

  • GC Brown A Bal-Price (2003) ArticleTitleInflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria Mol Neurobiol 27 325–355 Occurrence Handle12845153 Occurrence Handle1:CAS:528:DC%2BD3sXmtVyktrY%3D Occurrence Handle10.1385/MN:27:3:325

    Article  PubMed  CAS  Google Scholar 

  • W Dauer S Przedborski (2003) ArticleTitleParkinson’s disease: mechanisms and models Neuron 39 889–909 Occurrence Handle12971891 Occurrence Handle1:CAS:528:DC%2BD3sXnsFait7o%3D Occurrence Handle10.1016/S0896-6273(03)00568-3

    Article  PubMed  CAS  Google Scholar 

  • AG Dervan CK Meshul M Beales GJ McBean C Moore S Totterdell AK Snyder GE Meredith (2004) ArticleTitleAstroglial plasticity and glutamate function in a chronic mouse model of Parkinson’s disease Exp Neurol 190 145–156 Occurrence Handle15473988 Occurrence Handle1:CAS:528:DC%2BD2cXotlClsL0%3D Occurrence Handle10.1016/j.expneurol.2004.07.004

    Article  PubMed  CAS  Google Scholar 

  • A Dienel L Hertz (2001) ArticleTitleGlucose and lactate metabolism during brain activation J Neurosci Res 66 824–838 Occurrence Handle11746408 Occurrence Handle1:CAS:528:DC%2BD3MXpt1SgtrY%3D Occurrence Handle10.1002/jnr.10079

    Article  PubMed  CAS  Google Scholar 

  • DA Di Monte I Tokar JW Langston (1999) ArticleTitleImpaired glutamate clearance as a consequence of energy failure caused by MPP+ in astrocytic cultures Toxicol Appl Pharmacol 158 296–302 Occurrence Handle10438663 Occurrence Handle1:CAS:528:DyaK1MXkvFKisLg%3D Occurrence Handle10.1006/taap.1999.8717

    Article  PubMed  CAS  Google Scholar 

  • A Doble (1999) ArticleTitleThe role of excitotoxicity in neurodegenerative disease: implications for therapy Pharmacol Ther 81 163–221 Occurrence Handle10334661 Occurrence Handle1:CAS:528:DyaK1MXhsFWlsrk%3D Occurrence Handle10.1016/S0163-7258(98)00042-4

    Article  PubMed  CAS  Google Scholar 

  • KL Double GM Halliday J Henderson FM Griffiths T Heinemann P Riederer M Gerlach (2003) ArticleTitleThe dopamine receptor agonist lisuride attenuates iron-mediated dopaminergic neurodegeneration Exp Neurol 184 530–535 Occurrence Handle14637122 Occurrence Handle1:CAS:528:DC%2BD3sXptVektLw%3D Occurrence Handle10.1016/j.expneurol.2003.08.006

    Article  PubMed  CAS  Google Scholar 

  • P Foley M Gerlach KL Double P Riederer (2004) ArticleTitleDopamine receptor agonists in the therapy of Parkinson’s disease J Neural Transm 111 1375–1446 Occurrence Handle15480844 Occurrence Handle1:CAS:528:DC%2BD2cXotFCrtbg%3D Occurrence Handle10.1007/s00702-003-0059-x

    Article  PubMed  CAS  Google Scholar 

  • A Favit MA Sortino G Aleppo U Scapapnini PL Canonico (1993) ArticleTitleProtection by dihydroergocryptine of glutamate-induced neurotoxicity Pharmacol Toxicol 73 24–28

    Google Scholar 

  • CE Gavin KK Gunter TE Gunter (1999) ArticleTitleManganese and calcium transport in mitochondria: implications for manganese toxicity Neurotoxicology 20 445–453 Occurrence Handle10385903 Occurrence Handle1:CAS:528:DyaK1MXktFemu7g%3D

    PubMed  CAS  Google Scholar 

  • M Gerlach K Double H Reichmann P Riederer (2003) ArticleTitleArguments for the use of dopamine receptor agonists in clinical and preclinical Parkinson’s disease J Neural Transm (Suppl) 65 167–183

    Google Scholar 

  • G Gille WD Rausch ST Hung R Moldzio A Ngyuen B Janetzky A Engfer H Reichmann (2002) ArticleTitleProtection of dopaminergic neurons in primary culture by lisuride J Neural Transm 109 157–169 Occurrence Handle12075855 Occurrence Handle1:CAS:528:DC%2BD38XjsF2ls7g%3D Occurrence Handle10.1007/s007020200011

    Article  PubMed  CAS  Google Scholar 

  • M Gomez-Vargas S Nishibayashi-Asanuma M Asanuma Y Kondo E Iwata N Ogawa (1998) ArticleTitlePergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain Brain Res 790 202–208 Occurrence Handle9593894 Occurrence Handle1:CAS:528:DyaK1cXjtVGrt7s%3D Occurrence Handle10.1016/S0006-8993(97)01521-7

    Article  PubMed  CAS  Google Scholar 

  • JB Gramsbergen G Leegsma-Vogt K Venema J Noraberg J Korf (2003) ArticleTitleQuantitative on-line monitoring of hippocampus glucose and lactate metabolism in organotypic cultures using biosensor technology J Neurochem 85 399–408 Occurrence Handle12675916 Occurrence Handle1:CAS:528:DC%2BD3sXjtlylsrk%3D

    PubMed  CAS  Google Scholar 

  • L Had-Aissouni DB Re A Nieoullon L Kerkerian-Le Goff (2002) ArticleTitleImportance of astrocytic inactivation of synaptically released glutamate for cell survival in the central nervous system – are astrocytes vulnerable to low intracellular glutamate concentrations? J Physiol Paris 96 317–322 Occurrence Handle12445912 Occurrence Handle1:CAS:528:DC%2BD38XoslGhsbk%3D Occurrence Handle10.1016/S0928-4257(02)00022-0

    Article  PubMed  CAS  Google Scholar 

  • Y Huang L Cheung D Rowe G Halliday (2004) ArticleTitleGenetic contributions to Parkinson’s disease Brain Res Brain Res Rev 46 44–70 Occurrence Handle15297154 Occurrence Handle1:CAS:528:DC%2BD2cXmsVGit7k%3D Occurrence Handle10.1016/j.brainresrev.2004.04.007

    Article  PubMed  CAS  Google Scholar 

  • RM Hollingworth KI Ahammadsahib G Gadelhak JL McLaughlin (1994) ArticleTitleNew inhibitors of complex I of the mitochondrial electron transport chain with activity as pesticides Biochem Soc Trans 22 230–233 Occurrence Handle8206238 Occurrence Handle1:CAS:528:DyaK2cXitlyjurg%3D

    PubMed  CAS  Google Scholar 

  • SO Jacobsson CJ Fowler (1999) ArticleTitleDopamine and glutamate neurotoxicity in cultured chick telencephalic cells: effects of NMDA antagonists, antioxidants and MAO inhibitors Neurochem Int 34 49–62 Occurrence Handle10100196 Occurrence Handle1:CAS:528:DyaK1MXhslCgsb4%3D Occurrence Handle10.1016/S0197-0186(98)00069-2

    Article  PubMed  CAS  Google Scholar 

  • P Jenner (2003) ArticleTitleOxidative stress in Parkinson’s disease Ann Neurol 53 IssueIDSuppl 3 26–36 Occurrence Handle10.1002/ana.10483 Occurrence Handle1:CAS:528:DC%2BD3sXjtFGitLs%3D

    Article  CAS  Google Scholar 

  • Koutsilieri E, Scheller C, Grunblatt E, Nara K, Li J, Riederer P (2002) Free radicals in Parkinson’s disease. J Neurol 249 (Suppl 2): II 01–05

    Google Scholar 

  • S Kuzuhara H Mori N Izumiyama M Yoshimura Y Ihara (1988) ArticleTitleLewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study Acta Neuropathol (Berl) 75 345–353 Occurrence Handle1:CAS:528:DyaL1cXhs1GlsL8%3D Occurrence Handle10.1007/BF00687787

    Article  CAS  Google Scholar 

  • LP Liang YS Ho M Patel (2000) ArticleTitleMitochondrial superoxide production in kainate-induced hippocampal damage Neuroscience 101 563–570 Occurrence Handle11113305 Occurrence Handle1:CAS:528:DC%2BD3cXosFemtrw%3D Occurrence Handle10.1016/S0306-4522(00)00397-3

    Article  PubMed  CAS  Google Scholar 

  • I Miyazaki M Asanuma FJ Diaz-Corrales K Miyoshi N Ogawa (2004) ArticleTitleDirect evidence for expression of dopamine receptors in astrocytes from basal ganglia Brain Res 1029 120–123 Occurrence Handle15533323 Occurrence Handle1:CAS:528:DC%2BD2cXpsFSqtbk%3D Occurrence Handle10.1016/j.brainres.2004.09.014

    Article  PubMed  CAS  Google Scholar 

  • TH Murphy M Miyamoto A Sastre RL Schnaar JT Coyle (1989) ArticleTitleGlutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress Neuron 2 1547–1558 Occurrence Handle2576375 Occurrence Handle1:CAS:528:DyaK3cXltV2ksrg%3D Occurrence Handle10.1016/0896-6273(89)90043-3

    Article  PubMed  CAS  Google Scholar 

  • A Oka MJ Belliveau PA Rosenberg JJ Volpe (1993) ArticleTitleVulnerability of oligodendroglia to glutamate: pharmacology, mechanisms, and prevention J Neurosci 13 1441–1453 Occurrence Handle8096541 Occurrence Handle1:CAS:528:DyaK3sXks1Gis7s%3D

    PubMed  CAS  Google Scholar 

  • CW Olanow (2002) ArticleTitleThe role of dopamine agonists in the treatment of early Parkinson’s disease Neurology 58 IssueIDSuppl 1 S33–S41 Occurrence Handle11909983 Occurrence Handle1:CAS:528:DC%2BD38Xit1Wntbc%3D

    PubMed  CAS  Google Scholar 

  • M Patel BJ Day JD Crapo I Fridovich JO McNamara (1996) ArticleTitleRequirement for superoxide in excitotoxic cell death Neuron 16 345–355 Occurrence Handle8789949 Occurrence Handle1:CAS:528:DyaK28XhtlGhsLc%3D Occurrence Handle10.1016/S0896-6273(00)80052-5

    Article  PubMed  CAS  Google Scholar 

  • Plaitakis A, Shashidharan P (2000) Glutamate transport and metabolism in dopaminergic neurons of substantia nigra: implications for the pathogenesis of Parkinson’s disease. J Neurol 247 (Suppl 2) II 25–35

    Google Scholar 

  • MS Pollanen DW Dickson C Bergeron (1993) ArticleTitlePathology and biology of the Lewy body J Neuropathol Exp Neurol 52 183–191 Occurrence Handle7684074 Occurrence Handle1:STN:280:DyaK3s3mtVCrsA%3D%3D Occurrence Handle10.1097/00005072-199305000-00001

    Article  PubMed  CAS  Google Scholar 

  • MH Polymeropoulos JJ Higgins LI Golbe WG Johnson SE Ide G Di Iorio G Sanges ES Stenroos LT Pho AA Schaffer AM Lazzarini RL Nussbaum RC Duvoisin (1996) ArticleTitleMapping of a gene for Parkinson’s disease to chromosome 4q21–q23 Science 274 1197–1199 Occurrence Handle8895469 Occurrence Handle1:CAS:528:DyaK28XmvVyit74%3D Occurrence Handle10.1126/science.274.5290.1197

    Article  PubMed  CAS  Google Scholar 

  • K Radad G Gille R Moldzio H Saito WD Rausch (2004a) ArticleTitleGinsenosides Rb1 and Rg1 effects on mesencephalic dopaminergic cells stressed with glutamate Brain Res 1021 41–53 Occurrence Handle1:CAS:528:DC%2BD2cXmvFWkur4%3D Occurrence Handle10.1016/j.brainres.2004.06.030

    Article  CAS  Google Scholar 

  • K Radad G Gille R Moldzio H Saito K Ishige WD Rausch (2004b) ArticleTitleGinsenosides Rb1 and Rg1 effects on survival and neurite growth of MPP+-affected mesencephalic dopaminergic cells J Neural Transm 111 37–45 Occurrence Handle1:CAS:528:DC%2BD2cXhtlGktQ%3D%3D Occurrence Handle10.1007/s00702-003-0063-1

    Article  CAS  Google Scholar 

  • P Riederer H Reichmann B Janetzky J Sian KP Lesch KW Lange KL Double T Nagatsu M Gerlach (2001) ArticleTitleNeural degeneration in Parkinson’s disease Adv Neurol 86 125–136 Occurrence Handle11553969 Occurrence Handle1:CAS:528:DC%2BD3MXjvFKiu7Y%3D

    PubMed  CAS  Google Scholar 

  • MC Rodriguez JA Obeso CW Olanow (1998) ArticleTitleSubthalamic nucleus-mediated excitotoxicity in Parkinson’s disease: a target for neuroprotection Ann Neurol 44 IssueIDSuppl 1 S175–S188 Occurrence Handle9749591 Occurrence Handle1:CAS:528:DyaK1cXmtFGktLY%3D

    PubMed  CAS  Google Scholar 

  • KM Savolainen J Loikkanen J Naarala (1995) ArticleTitleAmplification of glutamate-induced oxidative stress Toxicol Lett 82/83 399–405 Occurrence Handle1:CAS:528:DyaK28Xht1Wrsbs%3D Occurrence Handle10.1016/0378-4274(95)03490-0

    Article  CAS  Google Scholar 

  • T Shang S Kotamraju SV Kalivendi CJ Hillard B Kalyanaraman (2004) ArticleTitle1-Methyl-4-phenylpyridinium-inuced apoptosis in cerebellar granule neurons is mediated by transferring receptor iron-dependent depletion of tetrahydrobiopterin and neuronal nitric-oxide synthase-derived superoxide J Biol Chem 279 19099–19112 Occurrence Handle14752097 Occurrence Handle1:CAS:528:DC%2BD2cXjsVKmtLk%3D Occurrence Handle10.1074/jbc.M400101200

    Article  PubMed  CAS  Google Scholar 

  • G Shanker M Aschner (2001) ArticleTitleIdentification and characterization of uptake systems for cystine and cysteine in cultured astrocytes and neurons: evidence for methylmercury-targeted disruption of astrocyte transport J Neurosci Res 66 998–1002 Occurrence Handle11746429 Occurrence Handle1:CAS:528:DC%2BD3MXpt1SgtLc%3D Occurrence Handle10.1002/jnr.10066

    Article  PubMed  CAS  Google Scholar 

  • TB Sherer R Betarbet JT Greenamyre (2002) ArticleTitleEnvironment, mitochondria and Parkinson’s disease The Neuroscientist 8 192–197 Occurrence Handle12061498 Occurrence Handle1:CAS:528:DC%2BD38XkvF2ntLw%3D

    PubMed  CAS  Google Scholar 

  • S Tan D Schubert P Maher (2001) ArticleTitleOxytosis: a novel form of programmed cell death Curr Top Med Chem 1 497–506 Occurrence Handle11895126 Occurrence Handle1:CAS:528:DC%2BD3MXos1aitrc%3D Occurrence Handle10.2174/1568026013394741

    Article  PubMed  CAS  Google Scholar 

  • R Tintner J Jankovic (2003) ArticleTitleDopamine agonists in Parkinson’s disease Expert Opin Invest Drugs 12 1803–1820 Occurrence Handle1:CAS:528:DC%2BD3sXosVGnt7k%3D Occurrence Handle10.1517/13543784.12.11.1803

    Article  CAS  Google Scholar 

  • MJ Tsai EHY Lee (1998) ArticleTitleNitric oxide donors protect cultured rat astrocytes from 1-methyl-4-phenylpyridinium-induced toxicity Free Radic Biol Med 24 705–713 Occurrence Handle9586799 Occurrence Handle1:CAS:528:DyaK1cXivFGhsbs%3D Occurrence Handle10.1016/S0891-5849(97)00329-8

    Article  PubMed  CAS  Google Scholar 

  • S Vesce L Kirk DG Nicholls (2004) ArticleTitleRelationship between superoxide levels and delayed calcium deregulation in cultured cerebellar granule cells exposed continuously to glutamate J Neurochem 90 683–693 Occurrence Handle15255947 Occurrence Handle1:CAS:528:DC%2BD2cXmsFertrY%3D Occurrence Handle10.1111/j.1471-4159.2004.02516.x

    Article  PubMed  CAS  Google Scholar 

  • SS Wong RHY Li A Stadlin (1999) ArticleTitleOxidative stress induced by MPTP and MPP+: selective vulnerability of cultured mouse astrocytes Brain Res 836 237–244 Occurrence Handle10415427 Occurrence Handle1:CAS:528:DyaK1MXks1Cktrg%3D Occurrence Handle10.1016/S0006-8993(99)01661-3

    Article  PubMed  CAS  Google Scholar 

  • M Yoshioka K Tanaka I Miyazaki N Fujita Y Higashi M Asanuma N Ogawa (2002) ArticleTitleThe dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals Neurosci Res 43 259–267 Occurrence Handle12103444 Occurrence Handle1:CAS:528:DC%2BD38XkvFyltrg%3D Occurrence Handle10.1016/S0168-0102(02)00040-8

    Article  PubMed  CAS  Google Scholar 

  • BT Zhu (2004) ArticleTitleCNS dopamine oxidation and catechol-O-methyltransferase: importance in the etiology, pharmacotherapy, and dietary prevention of Parkinson’s disease Int J Mol Med 13 343–353 Occurrence Handle14767563 Occurrence Handle1:CAS:528:DC%2BD2cXitFamsr0%3D

    PubMed  CAS  Google Scholar 

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  1. Institute for Medical Chemistry, DNS, University for Veterinary Medicine, Vienna, Austria

    R. Moldzio, K. Radad, J. C. Duvigneau, B. Kranner, C. Krewenka, C. Piskernik & W. D. Rausch

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  1. R. Moldzio
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  2. K. Radad
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  3. J. C. Duvigneau
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  4. B. Kranner
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  5. C. Krewenka
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  6. C. Piskernik
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  7. W. D. Rausch
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Moldzio, R., Radad, K., Duvigneau, J. et al. Glutamate-induced cell death and formation of radicals can be reduced by lisuride in mesencephalic primary cell culture. J Neural Transm 113, 1095–1105 (2006). https://doi.org/10.1007/s00702-005-0394-1

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