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Molecular and Cellular Biochemistry

, Volume 442, Issue 1–2, pp 129–142 | Cite as

Treatment with pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) differently affects survival, locomotor activity, and biochemical markers in Drosophila melanogaster

  • Deividi C. S. Soares
  • José L. R. Portela
  • Daniel H. Roos
  • Nathane R. Rodrigues
  • Karen K. Gomes
  • Giulianna E. Macedo
  • Thais Posser
  • Jeferson L. Franco
  • Waseem Hassan
  • Robson L. Puntel
Article

Abstract

PTZ is a convulsive agent that acts via selective blockage of GABAA receptor channels, whereas 4-AP leads to a convulsive episode via blockage of K+ channels. However, the mechanism(s) by which pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) cause toxicity to Drosophila melanogaster needs to be properly explored, once it will help in establishing an alternative model for development of proper therapeutic strategies and also to counteract the changes associated with exposure to both epileptic drugs. For the purpose, we investigated the effects of exposure (48 h) to PTZ (60 mM) and/or 4-AP (20 mM) on survival, locomotor performance, and biochemical markers in the body and/or head of flies. 4-AP-fed flies presented a higher incidence of mortality and a worse performance in the open field test as compared to non-treated flies. 4-AP also caused a significant increase in the reactive species (RS) and protein carbonyl (PC) content in the body and head. Also a significant increase in catalase and acetylcholinesterase (AChE) activities was observed in the body. In the same vein, PTZ exposure resulted in a significant increase in RS, thiobarbituric acid reactive substances (TBARS), PC content, and catalase activity in the body. PTZ exposure also caused a significant increase in AChE activity both in body and head. It is important to note that PTZ-treated flies also down-regulated the NRF2 expression. Moreover, both 4AP- and PTZ-fed flies presented a significant decrease in MTT reduction, down-regulation, and inhibition of SOD in body. However, SOD was significantly more active in the head of both 4-AP and PTZ-treated flies. Our findings provide evidence regarding the toxicological potential of both PTZ and/or 4-AP to flies. This model will help in decoding the underlying toxicological mechanisms of the stated drugs. It will also help to properly investigate the therapeutic strategies and to counteract the drastic changes associated with both epileptogenic drugs.

Keywords

Epileptogenic drugs Oxidative stress Enzyme activity Gene expression 

Notes

Acknowledgements

The authors are grateful to FAPERGS, CAPES, CNPq, FINEP, INCT-EN, and UNIPAMPA. Additional support was provided by CNPq/FAPERGS/DECIT/SCTIE-MS/PRONEM #11/2029-1 and CNPq (Universal) research grants # 449428/2014-1 and # 456207/2014-7. DCSS and JLP are grateful to CAPES for the scholarship.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. 1.
    Martinc B, Grabnar I, Vovk T (2014) Antioxidants as a preventive treatment for epileptic process: a review of the current status. Curr Neuropharmacol 12:527–550. doi: 10.2174/1570159X12666140923205715 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Mehla J, Reeta KH, Gupta P, Gupta YK (2010) Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model. Life Sci 87:596–603. doi: 10.1016/j.lfs.2010.09.006 CrossRefPubMedGoogle Scholar
  3. 3.
    Stewart AM, Desmond D, Kyzar E, Gaikwad S, Roth A, Riehl R, Collins C, Monnig L, Green J, Kalueff AV (2012) Perspectives of zebrafish models of epilepsy: what, how and where next? Brain Res Bull 87:135–143. doi: 10.1016/j.brainresbull.2011.11.020 CrossRefPubMedGoogle Scholar
  4. 4.
    White HS (2002) Animal models of epileptogenesis. Neurology 59:S7–S14CrossRefPubMedGoogle Scholar
  5. 5.
    Takechi K, Suemaru K, Kawasaki H, Araki H (2012) Impaired memory following repeated pentylenetetrazol treatments in kindled mice. Yakugaku Zasshi 132:179–182CrossRefPubMedGoogle Scholar
  6. 6.
    Ferando I, Mody I (2012) GABAA receptor modulation by neurosteroids in models of temporal lobe epilepsies. Epilepsia 53(Suppl 9):89–101. doi: 10.1111/epi.12038 CrossRefPubMedGoogle Scholar
  7. 7.
    Eloqayli H, Dahl CB, Gotestam KG, Unsgard G, Hadidi H, Sonnewald U (2003) Pentylenetetrazole decreases metabolic glutamate turnover in rat brain. J Neurochem 85:1200–1207CrossRefPubMedGoogle Scholar
  8. 8.
    Yudkoff M, Daikhin Y, Nissim I, Horyn O, Lazarow A, Nissim I (2003) Metabolism of brain amino acids following pentylenetetrazole treatment. Epilepsy Res 53:151–162CrossRefPubMedGoogle Scholar
  9. 9.
    Buckingham SD, Hosie AM, Roush RL, Sattelle DB (1994) Actions of agonists and convulsant antagonists on a Drosophila melanogaster GABA receptor (Rdl) homo-oligomer expressed in Xenopus oocytes. Neurosci Lett 181:137–140CrossRefPubMedGoogle Scholar
  10. 10.
    Stilwell GE, Saraswati S, Littleton JT, Chouinard SW (2006) Development of a Drosophila seizure model for in vivo high-throughput drug screening. Eur J Neurosci 24:2211–2222. doi: 10.1111/j.1460-9568.2006.05075.x CrossRefPubMedGoogle Scholar
  11. 11.
    Gonzalez-Sulser A, Wang J, Queenan BN, Avoli M, Vicini S, Dzakpasu R (2012) Hippocampal neuron firing and local field potentials in the in vitro 4-aminopyridine epilepsy model. J Neurophysiol 108:2568–2580. doi: 10.1152/jn.00363.2012 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Laura MC, Xochitl FP, Anne S, Alberto MV (2015) Analysis of connexin expression during seizures induced by 4-aminopyridine in the rat hippocampus. J Biomed Sci 22:69. doi: 10.1186/s12929-015-0176-5 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wang JW, Wu CF (1996) In vivo functional role of the Drosophila hyperkinetic beta subunit in gating and inactivation of Shaker K+ channels. Biophys J 71:3167–3176. doi: 10.1016/S0006-3495(96)79510-3 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Zhao ML, Sable EO, Iverson LE, Wu CF (1995) Functional expression of Shaker K+ channels in cultured Drosophila “giant” neurons derived from Sh cDNA transformants: distinct properties, distribution, and turnover. J Neurosci 15:1406–1418PubMedGoogle Scholar
  15. 15.
    Yao WD, Wu CF (1999) Auxiliary Hyperkinetic beta subunit of K+ channels: regulation of firing properties and K+ currents in Drosophila neurons. J Neurophysiol 81:2472–2484CrossRefPubMedGoogle Scholar
  16. 16.
    Pena F, Tapia R (2000) Seizures and neurodegeneration induced by 4-aminopyridine in rat hippocampus in vivo: role of glutamate- and GABA-mediated neurotransmission and of ion channels. Neuroscience 101:547–561CrossRefPubMedGoogle Scholar
  17. 17.
    Tapia R, Sitges M, Morales E (1985) Mechanism of the calcium-dependent stimulation of transmitter release by 4-aminopyridine in synaptosomes. Brain Res 361:373–382CrossRefPubMedGoogle Scholar
  18. 18.
    Brito VB, Rocha JB, Folmer V, Erthal F (2009) Diphenyl diselenide and diphenyl ditelluride increase the latency for 4-aminopyridine-induced chemical seizure and prevent death in mice. Acta Biochim Pol 56:125–134PubMedGoogle Scholar
  19. 19.
    Folbergrova J (2013) Oxidative stress in immature brain following experimentally-induced seizures. Physiol Res 62(Suppl 1):S39–S48PubMedGoogle Scholar
  20. 20.
    Folbergrova J, Kunz WS (2012) Mitochondrial dysfunction in epilepsy. Mitochondrion 12:35–40. doi: 10.1016/j.mito.2011.04.004 CrossRefPubMedGoogle Scholar
  21. 21.
    Ikonomidou C, Kaindl AM (2011) Neuronal death and oxidative stress in the developing brain. Antioxid Redox Signal 14:1535–1550. doi: 10.1089/ars.2010.3581 CrossRefPubMedGoogle Scholar
  22. 22.
    Lin JJ, Mula M, Hermann BP (2012) Uncovering the neurobehavioural comorbidities of epilepsy over the lifespan. Lancet 380:1180–1192. doi: 10.1016/S0140-6736(12)61455-X CrossRefPubMedGoogle Scholar
  23. 23.
    Patel M (2004) Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures. Free Radic Biol Med 37:1951–1962. doi: 10.1016/j.freeradbiomed.2004.08.021 CrossRefPubMedGoogle Scholar
  24. 24.
    Waldbaum S, Patel M (2010) Mitochondria, oxidative stress, and temporal lobe epilepsy. Epilepsy Res 88:23–45. doi: 10.1016/j.eplepsyres.2009.09.020 CrossRefPubMedGoogle Scholar
  25. 25.
    Loscher W (2011) Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure 20:359–368. doi: 10.1016/j.seizure.2011.01.003 CrossRefPubMedGoogle Scholar
  26. 26.
    Mohammad F, Singh P, Sharma A (2009) A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs. BMC Syst Biol 3:11. doi: 10.1186/1752-0509-3-11 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Benton R (2008) Chemical sensing in Drosophila. Curr Opin Neurobiol 18:357–363. doi: 10.1016/j.conb.2008.08.012 CrossRefPubMedGoogle Scholar
  28. 28.
    Hirth F (2010) Drosophila melanogaster in the study of human neurodegeneration. CNS Neurol Disord 9:504–523CrossRefGoogle Scholar
  29. 29.
    Marley R, Baines RA (2011) Increased persistent Na+ current contributes to seizure in the slamdance bang-sensitive Drosophila mutant. J Neurophysiol 106:18–29. doi: 10.1152/jn.00808.2010 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Jeibmann A, Paulus W (2009) Drosophila melanogaster as a model organism of brain diseases. Int J Mol Sci 10:407–440. doi: 10.3390/ijms10020407 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Parker L, Howlett IC, Rusan ZM, Tanouye MA (2011) Seizure and epilepsy: studies of seizure disorders in Drosophila. Int Rev Neurobiol 99:1–21. doi: 10.1016/B978-0-12-387003-2.00001-X CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Adedara IA, Abolaji AO, Rocha JB, Farombi EO (2016) Diphenyl diselenide protects against mortality, locomotor deficits and oxidative stress in Drosophila melanogaster model of manganese-induced neurotoxicity. Neurochem Res 41:1430–1438. doi: 10.1007/s11064-016-1852-x CrossRefPubMedGoogle Scholar
  33. 33.
    Bianchini MC, Gularte CO, Escoto DF, Pereira G, Gayer MC, Roehrs R, Soares FA, Puntel RL (2016) Peumus boldus (Boldo) aqueous extract present better protective effect than boldine against manganese-induced toxicity in D. melanogaster. Neurochem Res 41:2699–2707. doi: 10.1007/s11064-016-1984-z CrossRefPubMedGoogle Scholar
  34. 34.
    Feany MB, Bender WW (2000) A Drosophila model of Parkinson’s disease. Nature 404:394–398. doi: 10.1038/35006074 CrossRefPubMedGoogle Scholar
  35. 35.
    Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358CrossRefPubMedGoogle Scholar
  36. 36.
    Levine RL, Wehr N, Williams JA, Stadtman ER, Shacter E (2000) Determination of carbonyl groups in oxidized proteins. Methods Mol Biol 99:15–24. doi: 10.1385/1-59259-054-3:15 PubMedGoogle Scholar
  37. 37.
    Perez-Severiano F, Santamaria A, Pedraza-Chaverri J, Medina-Campos ON, Rios C, Segovia J (2004) Increased formation of reactive oxygen species, but no changes in glutathione peroxidase activity, in striata of mice transgenic for the Huntington’s disease mutation. Neurochem Res 29:729–733CrossRefPubMedGoogle Scholar
  38. 38.
    Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77CrossRefPubMedGoogle Scholar
  39. 39.
    Lushchak VI, Bagnyukova TV, Husak VV, Luzhna LI, Lushchak OV, Storey KB (2005) Hyperoxia results in transient oxidative stress and an adaptive response by antioxidant enzymes in goldfish tissues. Int J Biochem Cell Biol 37:1670–1680. doi: 10.1016/j.biocel.2005.02.024 CrossRefPubMedGoogle Scholar
  40. 40.
    Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126CrossRefPubMedGoogle Scholar
  41. 41.
    Ellman GL, Courtney KD, Andres V, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95CrossRefPubMedGoogle Scholar
  42. 42.
    Hosamani R (2009) Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster. Neurotoxicology 30:977–985. doi: 10.1016/j.neuro.2009.08.012 CrossRefPubMedGoogle Scholar
  43. 43.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408. doi: 10.1006/meth.2001.1262 CrossRefPubMedGoogle Scholar
  44. 44.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMedGoogle Scholar
  45. 45.
    Littleton JT, Ganetzky B (2000) Ion channels and synaptic organization: analysis of the Drosophila genome. Neuron 26:35–43CrossRefPubMedGoogle Scholar
  46. 46.
    Pandey UB, Nichols CD (2011) Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev 63:411–436. doi: 10.1124/pr.110.003293 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Epel ES, Lithgow GJ (2014) Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity. J Gerontol A 69(Suppl 1):S10–S16. doi: 10.1093/gerona/glu055 CrossRefGoogle Scholar
  48. 48.
    Martin JR (2004) A portrait of locomotor behaviour in Drosophila determined by a video-tracking paradigm. Behav Processes 67:207–219. doi: 10.1016/j.beproc.2004.04.003 CrossRefPubMedGoogle Scholar
  49. 49.
    Wang P, Saraswati S, Guan Z, Watkins CJ, Wurtman RJ, Littleton JT (2004) A Drosophila temperature-sensitive seizure mutant in phosphoglycerate kinase disrupts ATP generation and alters synaptic function. J Neurosci 24:4518–4529. doi: 10.1523/JNEUROSCI.0542-04.2004 CrossRefPubMedGoogle Scholar
  50. 50.
    Chang HY, Grygoruk A, Brooks ES, Ackerson LC, Maidment NT, Bainton RJ, Krantz DE (2006) Overexpression of the Drosophila vesicular monoamine transporter increases motor activity and courtship but decreases the behavioral response to cocaine. Mol Psychiatry 11:99–113. doi: 10.1038/sj.mp.4001742 CrossRefPubMedGoogle Scholar
  51. 51.
    Caughlan A, Newhouse K, Namgung U, Xia Z (2004) Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases. Toxicol Sci 78:125–134. doi: 10.1093/toxsci/kfh038 CrossRefPubMedGoogle Scholar
  52. 52.
    Sudati JH, Vieira FA, Pavin SS, Dias GR, Seeger RL, Golombieski R, Athayde ML, Soares FA, Rocha JB, Barbosa NV (2013) Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster. Neurotoxicology 37:118–126. doi: 10.1016/j.neuro.2013.04.006 CrossRefPubMedGoogle Scholar
  53. 53.
    Takahashi S, Abe T, Gotoh J, Fukuuchi Y (2002) Substrate-dependence of reduction of MTT: a tetrazolium dye differs in cultured astroglia and neurons. Neurochem Int 40:441–448CrossRefPubMedGoogle Scholar
  54. 54.
    Wang S, Yu H, Wickliffe JK (2011) Limitation of the MTT and XTT assays for measuring cell viability due to superoxide formation induced by nano-scale TiO2. Toxicol In Vitro 25:2147–2151. doi: 10.1016/j.tiv.2011.07.007 CrossRefPubMedGoogle Scholar
  55. 55.
    Bibi F, Ullah I, Kim MO, Naseer MI (2017) Metformin attenuate PTZ-induced apoptotic neurodegeneration in human cortical neuronal cells. Pak J Med Sci 33:581–585. doi: 10.12669/pjms.333.11996 PubMedPubMedCentralGoogle Scholar
  56. 56.
    Fergestad T, Bostwick B, Ganetzky B (2006) Metabolic disruption in Drosophila bang-sensitive seizure mutants. Genetics 173:1357–1364. doi: 10.1534/genetics.106.057463 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Boiko N, Kucher V, Eaton BA, Stockand JD (2013) Inhibition of neuronal degenerin/epithelial Na+ channels by the multiple sclerosis drug 4-aminopyridine. J Biol Chem 288:9418–9427. doi: 10.1074/jbc.M112.449413 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Zhang Y, Du Y, Jiang D, Behnke C, Nomura Y, Zhorov BS, Dong K (2016) The receptor site and mechanism of action of sodium channel blocker insecticides. J Biol Chem 291:20113–20124. doi: 10.1074/jbc.M116.742056 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Ilhan A, Gurel A, Armutcu F, Kamisli S, Iraz M (2005) Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazol-induced kindling in mice. Neuropharmacology 49:456–464. doi: 10.1016/j.neuropharm.2005.04.004 CrossRefPubMedGoogle Scholar
  60. 60.
    de Oliveira CC, de Oliveira CV, Grigoletto J, Ribeiro LR, Funck VR, Grauncke AC, de Souza TL, Souto NS, Furian AF, Menezes IR, Oliveira MS (2016) Anticonvulsant activity of beta-caryophyllene against pentylenetetrazol-induced seizures. Epilepsy Behav 56:26–31. doi: 10.1016/j.yebeh.2015.12.040 CrossRefPubMedGoogle Scholar
  61. 61.
    Golechha M, Bhatia J, Arya DS (2010) Hydroalcoholic extract of Emblica officinalis Gaertn. affords protection against PTZ-induced seizures, oxidative stress and cognitive impairment in rats. Indian J Exp Biol 48:474–478PubMedGoogle Scholar
  62. 62.
    Ribeiro MC, de Avila DS, Schneider CY, Hermes FS, Furian AF, Oliveira MS, Rubin MA, Lehmann M, Krieglstein J, Mello CF (2005) alpha-Tocopherol protects against pentylenetetrazol- and methylmalonate-induced convulsions. Epilepsy Res 66:185–194. doi: 10.1016/j.eplepsyres.2005.08.005 CrossRefPubMedGoogle Scholar
  63. 63.
    Sharma V, Nehru B, Munshi A, Jyothy A (2010) Antioxidant potential of curcumin against oxidative insult induced by pentylenetetrazol in epileptic rats. Methods Find Exp Clin Pharmacol 32:227–232. doi: 10.1358/mf.2010.32.4.1452090 CrossRefPubMedGoogle Scholar
  64. 64.
    Xie T, Wang WP, Mao ZF, Qu ZZ, Luan SQ, Jia LJ, Kan MC (2012) Effects of epigallocatechin-3-gallate on pentylenetetrazole-induced kindling, cognitive impairment and oxidative stress in rats. Neurosci Lett 516:237–241. doi: 10.1016/j.neulet.2012.04.001 CrossRefPubMedGoogle Scholar
  65. 65.
    Zhen JL, Chang YN, Qu ZZ, Fu T, Liu JQ, Wang WP (2016) Luteolin rescues pentylenetetrazole-induced cognitive impairment in epileptic rats by reducing oxidative stress and activating PKA/CREB/BDNF signaling. Epilepsy Behav 57:177–184. doi: 10.1016/j.yebeh.2016.02.001 CrossRefPubMedGoogle Scholar
  66. 66.
    Ternes AP, Zemolin AP, da Cruz LC, da Silva GF, Saidelles AP, de Paula MT, Wagner C, Golombieski RM, Flores EM, Picoloto RS, Pereira AB, Franco JL, Posser T (2014) Drosophila melanogaster—an embryonic model for studying behavioral and biochemical effects of manganese exposure. EXCLI J 13:1239–1253PubMedPubMedCentralGoogle Scholar
  67. 67.
    Cruz LC, Ecker A, Dias RS, Seeger RL, Braga MM, Boligon AA, Martins IK, Costa-Silva DG, Barbosa NV, Canedo AD, Posser T, Franco JL (2016) Brazilian pampa biome honey protects against mortality, locomotor deficits and oxidative stress induced by hypoxia/reperfusion in adult Drosophila melanogaster. Neurochem Res 41:116–129. doi: 10.1007/s11064-015-1744-5 CrossRefPubMedGoogle Scholar
  68. 68.
    Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284:13291–13295. doi: 10.1074/jbc.R900010200 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Patsoukis N, Zervoudakis G, Panagopoulos NT, Georgiou CD, Angelatou F, Matsokis NA (2004) Thiol redox state (TRS) and oxidative stress in the mouse hippocampus after pentylenetetrazol-induced epileptic seizure. Neurosci Lett 357:83–86. doi: 10.1016/j.neulet.2003.10.080 CrossRefPubMedGoogle Scholar
  70. 70.
    Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, Hong JS, Yoneda Y, Kim HC (2011) Role of oxidative stress in epileptic seizures. Neurochem Int 59:122–137. doi: 10.1016/j.neuint.2011.03.025 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Taiwe GS, Moto FC, Ayissi ER, Ngoupaye GT, Njapdounke JS, Nkantchoua GC, Kouemou N, Omam JP, Kandeda AK, Pale S, Pahaye D, Ngo Bum E (2015) Effects of a lyophilized aqueous extract of Feretia apodanthera Del. (Rubiaceae) on pentylenetetrazole-induced kindling, oxidative stress, and cognitive impairment in mice. Epilepsy Behav 43:100–108. doi: 10.1016/j.yebeh.2014.11.022 CrossRefPubMedGoogle Scholar
  72. 72.
    Pahuja M, Mehla J, Kumar Gupta Y (2012) Anticonvulsant and antioxidative activity of hydroalcoholic extract of tuber of Orchis mascula in pentylenetetrazole and maximal electroshock induced seizures in rats. J Ethnopharmacol 142:23–27. doi: 10.1016/j.jep.2012.04.006 CrossRefPubMedGoogle Scholar
  73. 73.
    Choudhary KM, Mishra A, Poroikov VV, Goel RK (2013) Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post-pentylenetetrazole-kindled mice. Eur J Pharmacol 704:33–40. doi: 10.1016/j.ejphar.2013.02.012 CrossRefPubMedGoogle Scholar
  74. 74.
    Visweswari G, Prasad KS, Chetan PS, Lokanatha V, Rajendra W (2010) Evaluation of the anticonvulsant effect of Centella asiatica (gotu kola) in pentylenetetrazol-induced seizures with respect to cholinergic neurotransmission. Epilepsy Behav 17:332–335. doi: 10.1016/j.yebeh.2010.01.002 CrossRefPubMedGoogle Scholar
  75. 75.
    Serra M, Dazzi L, Cagetti E, Chessa MF, Pisu MG, Sanna A, Biggio G (1997) Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats. J Neurochem 68:313–318CrossRefPubMedGoogle Scholar
  76. 76.
    Meilleur S, Aznavour N, Descarries L, Carmant L, Mamer OA, Psarropoulou C (2003) Pentylenetetrazol-induced seizures in immature rats provoke long-term changes in adult hippocampal cholinergic excitability. Epilepsia 44:507–517CrossRefPubMedGoogle Scholar
  77. 77.
    Zhang X, Lu L, Liu S, Ye W, Wu J, Zhang X (2013) Acetylcholinesterase deficiency decreases apoptosis in dopaminergic neurons in the neurotoxin model of Parkinson’s disease. Int J Biochem Cell Biol 45:265–272. doi: 10.1016/j.biocel.2012.11.015 CrossRefPubMedGoogle Scholar
  78. 78.
    Craig LA, Hong NS, McDonald RJ (2011) Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev 35:1397–1409. doi: 10.1016/j.neubiorev.2011.03.001 CrossRefPubMedGoogle Scholar
  79. 79.
    Greenspan RJ, Finn JA Jr, Hall JC (1980) Acetylcholinesterase mutants in Drosophila and their effects on the structure and function of the central nervous system. J Comp Neurol 189:741–774. doi: 10.1002/cne.901890409 CrossRefPubMedGoogle Scholar
  80. 80.
    Krishna G (2016) Aqueous extract of tomato seeds attenuates rotenone-induced oxidative stress and neurotoxicity in Drosophila melanogaster. J Sci Food Agric 96:1745–1755. doi: 10.1002/jsfa.7281 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Deividi C. S. Soares
    • 1
  • José L. R. Portela
    • 1
  • Daniel H. Roos
    • 1
  • Nathane R. Rodrigues
    • 2
  • Karen K. Gomes
    • 2
  • Giulianna E. Macedo
    • 2
  • Thais Posser
    • 2
  • Jeferson L. Franco
    • 2
  • Waseem Hassan
    • 3
  • Robson L. Puntel
    • 1
  1. 1.Programa de Pós-Graduação em BioquímicaUniversidade Federal do PampaUruguaianaBrazil
  2. 2.Programa de Pós-Graduação em Ciências Biológicas, Interdisciplinary Center for Biotechnology ResearchUniversidade Federal do PampaSão GabrielBrazil
  3. 3.Institute of Chemical SciencesUniversity of PeshawarPeshawarPakistan

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