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Journal of Molecular Neuroscience

, Volume 59, Issue 2, pp 280–289 | Cite as

Modulation of Corpus Striatal Neurochemistry by Astrocytes and Vasoactive Intestinal Peptide (VIP) in Parkinsonian Rats

  • İbrahim Halil Yelkenli
  • Emel Ulupinar
  • Orhan Tansel Korkmaz
  • Erol Şener
  • Gökhan Kuş
  • Zeynep Filiz
  • Neşe TunçelEmail author
Article

Abstract

The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used in animal models of Parkinson’s disease. In various neurodegenerative diseases, astrocytes play direct, active, and critical roles in mediating neuronal survival and functions. Vasoactive intestinal peptide (VIP) has neurotrophic actions and modulates a number of astrocytic activities. In this study, the effects of VIP on the striatal neurochemistry were investigated in parkinsonian rats. Adult Sprague-Dawley rats were divided into sham-operated, unilaterally 6-OHDA–lesioned, and lesioned + VIP-administered (25 ng/kg i.p.) groups. VIP was first injected 1 h after the intrastriatal 6-OHDA microinjection and then every 2 days throughout 15 days. Extracellular striatal concentration of glutathione (GSH), gamma-aminobutyric acid (GABA), glutamate (GLU), and lactate were measured in microdialysates by high-performance liquid chromatography (HPLC). Quantification of GABA and activity dependent neuroprotective protein (ADNP)-expressing cells were determined by glutamic acid decarboxylase (GAD)/ADNP + glial fibrillary acidic protein (GFAP) double immunohistochemistry. Our results demonstrated that a 6-OHDA lesion significantly increased the density of astrocytes in the striatum and VIP treatment slightly reduced the gliosis. Extracellular concentration of GABA, GLU, and lactate levels did not change, but GSH level significantly increased in the striatum of parkinsonian rats. VIP treatment reduced GSH level comparable to sham-operated groups, but enhanced GABA and GLU levels. Our double labeling results showed that VIP primarily acts on neurons to increase ADNP and GAD expression for protection. These results suggest that, in the 6-OHDA-induced neurodegeneration model, astrocytes were possibly activated for forefront defensiveness by modulating striatal neurochemistry.

Keywords

VIP (vasoactive intestinal peptide) Parkinson’s disease GSH (glutathione) ADNP (activity dependent neuroprotective protein) GABA (gamma-aminobutyric acid) Astrocyte 

Notes

Acknowledgments

This study was supported by Eskisehir Osmangazi University Scientific Research Commission (Project Number: 20121128). The part of chemical analyses of the study was supported by Scientific Research Committee of Anadolu University, Project No. 1101S003.

Compliance with Ethical Standards

All experimental procedures were performed in accordance with protocols approved by the Institutional Animal Usage Committee of Osmangazi University Faculty of Medicine (Protocol number: 42/241). All efforts were made to minimize animal suffering and to reduce the number of animals used.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. Abarca J, Bustos G (1999) Differential regulation of glutamate, aspartate and γ-amino-butyrate release by N-methyl-d-aspartate receptors in rat striatum after partial and extensive lesions to the nigro-striatal dopamine pathway. Neurochem Int 35(1):19–33CrossRefPubMedGoogle Scholar
  2. Allaman I, Bélanger M, Magistretti PJ (2011) Astrocyte-neuron metabolic relationships: for better and for worse. Trends Neurosci 34(2):76–87CrossRefPubMedGoogle Scholar
  3. Angulo MC, Le MK, Kozlov AS, Charpak S, Audinat E (2008) GABA, a forgotten gliotransmitter. Prog Neurobiol 86(3):297–303CrossRefPubMedGoogle Scholar
  4. Bassan M, Zamostiano R, Davidson A, et al. (1999) Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. J Neurochem 72:1283–1293CrossRefPubMedGoogle Scholar
  5. Beggiato S, Antonelli T, Tomasini MC, et al. (2013) Kynurenic acid, by targeting α7 nicotinic acetylcholine receptors, modulates extracellular GABA levels in the rat striatum in vivo. Eur J Neurosci 37(9):1470–1477CrossRefPubMedGoogle Scholar
  6. Bélanger M, Magistretti PJ (2009) The role of astroglia in neuroprotection. Dialogues Clin Neurosci 11:281–295PubMedPubMedCentralGoogle Scholar
  7. Bélanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14(6):724–738CrossRefPubMedGoogle Scholar
  8. Berthet C (2009) Neuroprotective role of lactate after serebral ischemia. J Cereb Blood Flow Metab 29:1780–1789CrossRefPubMedGoogle Scholar
  9. Brenneman DE (2007) Neuroprotection: a comparative view of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Peptides 28:1720–1726CrossRefPubMedGoogle Scholar
  10. Brenneman DE, Gozes I (1996) A femtomolar-acting neuroprotective peptide. J Clin Invest 97(10):2299–2307CrossRefPubMedPubMedCentralGoogle Scholar
  11. Brenneman DE, Phillips TM, Festoff BW, Gozes I (1997) Identity of neurotrophic molecules released from astroglia by vasoactive intestinal peptide. Ann N Y Acad Sci 814:167–173CrossRefPubMedGoogle Scholar
  12. Brenneman DE, Hauser J, Neale E, et al. (1998) Activity-dependent neurotrophic factor: structure-activity relationships of femtomolar-acting peptides. J Pharmacol Exp Ther 285(2):619–627PubMedGoogle Scholar
  13. Colangelo AM, Alberghina L, Papa M (2014) Astrogliosis as a therapeutic target for neurodegenerative diseases. Neuroscience Letters. 565:59–64CrossRefPubMedGoogle Scholar
  14. Coray WT, Loike JD, Brionne TC, et al. (2003) Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 9(4):453–457CrossRefGoogle Scholar
  15. Cosgrave AS, McKay JS, Morris R, Quinn JP, Thippeswamy T (2009) Nitric oxide regulates activity-dependent neuroprotective protein (ADNP) in the dentate gyrus of the rodent model of kainic acid-induced seizure. J Mol Neurosci 39(1–2):9–21CrossRefPubMedGoogle Scholar
  16. Coulter DA, Tore E (2012) Astrocytic regulation of glutamate homeostasis in epilepsy. Glia 60(8):1215–1226CrossRefPubMedPubMedCentralGoogle Scholar
  17. Coune PG, Craveiro M, Gaugler MN, et al. (2013) An in vivo ultrahigh field 14.1 T (1) H-MRS study on 6-OHDA and α-synuclein-based rat models of Parkinson’s disease: GABA as an early disease marker. NMR Biomed 26(1):43–50CrossRefPubMedGoogle Scholar
  18. Delgado M, Ganea D (2003a) Neuroprotective effect of vasoactive intestinal peptide (VİP) in a mouse model of Parkinson’s disease by blocking microglial activation. FASEB J 17:944–946PubMedGoogle Scholar
  19. Delgado M, Ganea D (2003b) Vasoactive intestinal peptide prevents activated microglia induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma. FASEB J 17:1922–1924PubMedGoogle Scholar
  20. Dervan AG, Meshul CK, Beales M, et al. (2004) Astroglial plasticity and glutamate function in a chronic mouse model of Parkinson’s disease. Exp Neurol 190(1):145–156CrossRefPubMedGoogle Scholar
  21. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV (2004) Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24(9):2143–2155CrossRefPubMedGoogle Scholar
  22. Gan J, Qi C, Mao LM, Liu Z (2014) Changes in surface expression of N-methyl-D-aspartate receptors in the striatum in a rat model of Parkinson’s disease. Drug Des Deve Ther 17(8):165–173Google Scholar
  23. Gennet N, Herden C, Bubb VJ, Quinn JP, Kipar A (2008) Expression of activity-dependent neuroprotective protein in the brain of adult rats. Histol Histopathol 23(3):309–317PubMedGoogle Scholar
  24. Gozes I (2007) Activity-dependent neuroprotective protein: from gene to drug candidate. Pharmacol Ther 114:145–153CrossRefGoogle Scholar
  25. Gozes I (2012) Neuropeptide GPCRs in neuroendocrinology: the case of activity-dependent neuroprotectiveprotein (ADNP) Frontiers in endocrinology. Neuroendocrine Science 3(133):1–4Google Scholar
  26. Hallström Å, Carlsson A, Hillered L, Ungerstedt U (1989) Simultaneous determination of lactate, puruvate and ascorbate in microdialysis samples from rat brain, blood, fat and muscle using high performance liquid chromatography. J Pharmacol Toxicol Methods 22:113–124Google Scholar
  27. Haydon PG, Carmignoto G (2006) Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev 86(3):1009–1031CrossRefPubMedGoogle Scholar
  28. Héja L., Gabriella N., Orsolya K. et al. (2012) Astrocytes convert network excitation to tonic inhibition of neurons. BMC Biology http://www.biomedcentral.com/1741-7007/10/26
  29. Hossain MA, Weiner N (1995) Interaction of dopaminergic and GABAergic neurotransmission: impact of 6-hydroxydopamine lesions into the substantia nigra of rats. J Pharmacol Exp Ther 275(1):237–244PubMedGoogle Scholar
  30. Korkmaz OT, Tunçel N, Tunçel M, Oncü EM, Sahintürk V, Celik M (2010) Vasoactive intestinal peptide (VİP) treatment of parkinsonian rats increases thalamic gamma-aminobutyric acid (GABA) levels and alters the release of nerve growth factor (NGF) by mast cells. J Mol Neurosci 41(2):278–287CrossRefPubMedGoogle Scholar
  31. Korkmaz OT, Ay H, Ulupınar E, Tunçel N (2012) Vasoactive intestinal peptide enhances striatal plasticity and prevents dopaminergic cell loss in parkinsonian rats. J Mol Neurosci 48(3):565–573CrossRefPubMedGoogle Scholar
  32. Kouki OM, Pierrick G, Helene C, et al. (2007) Role of PACAP and VİP in astroglial functions. Peptides 28:1753–1760CrossRefGoogle Scholar
  33. Lee M, Schwab C, McGeer PL (2011a) Astrocytes are GABAergic cells that modulate microglial activity. Glia 59:152–165CrossRefPubMedGoogle Scholar
  34. Lee M, McGeer EG, McGeer PL (2011b) Mechanisms of GABA release from human astrocytes. Glia 59:1600–1611CrossRefPubMedGoogle Scholar
  35. Liberto CM, Albrecht PJ, Herx LM, Yong VW, Levison SW (2004) Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem 89(5):1092–1100CrossRefPubMedGoogle Scholar
  36. Lindefors N, Brodin E, Tossman U, Segovia J, Ungerstedt U (1989) Tissue levels and in vivo release of tachykinins and GABA in striatum and substantia nigra of rat brain after unilateral striatal dopamine denervation. Exp Brain Res 74(3):527–534CrossRefPubMedGoogle Scholar
  37. Lunn G, Hellwig LC (1998) Handbook of derivatization reactions for HPLC, amino acids. Wiley 625Google Scholar
  38. Mandel S, Spivak-Pohis I, Gozes I (2008) ADNP differential nucleus/cytoplasm localization in neurons suggests multiple roles in neuronal differentiation and maintenance. J Mol Neurosci 35(2):127–141CrossRefPubMedGoogle Scholar
  39. Miao Y, Qiu Y, Lin Y, Miao Z, Zhang J, Lu X (2011) Protection by pyruvate against glutamate neurotoxicity is mediated by astrocytes through a glutathione-dependent mechanism. Mol Biol Rep 38(5):3235–3242CrossRefPubMedGoogle Scholar
  40. Morales I, Rodriguez M (2012) Self-induced accumulation of glutamate in striatal astrocytes and basal ganglia excitotoxicity. Glia 60(10):1481–1494CrossRefPubMedGoogle Scholar
  41. Morris G, Anderson G, Dean O, et al. (2014) The glutathione system: a new drug target in neuroimmune disorders. Mol Neurobiol 50(3):1059–1084CrossRefPubMedGoogle Scholar
  42. Offen D, Sherki Y, Melamed E, Fridkin M, Brenneman DE, Gozes I (2000) Vasoactive intestinal peptide (VİP) prevents neurotoxicity in neuronal cultures: relevance to neuroprotection in Parkinson’s disease. Brain Res 854:257–262CrossRefPubMedGoogle Scholar
  43. Orellana J.A., Stehberg J. (2014) Hemichannels: new roles in astroglial function Frontiers in Physiology Membrane Physiology and Membrane Biophysics. 5: Art. 193Google Scholar
  44. Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates. Academic, New YorkGoogle Scholar
  45. Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization proc. Natl Acad Sci USA Neurobiology 91:10625–10629CrossRefGoogle Scholar
  46. Pellerin L, Magistretti PJ (2012) Sweet sixteen for ANLS. Journal of Cerebral Blood Flow & Metabolism. 32:1152–1166CrossRefGoogle Scholar
  47. Pellerin L, Bouzier-Sore AK, Aubert A, et al. (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251–1262CrossRefPubMedGoogle Scholar
  48. Pinhasov A, Shmuel MS, Arkady TA, et al. (2003) Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Dev Brain Res 143:83–90Google Scholar
  49. Rappold MP, Tieu K (2010) Astrocytes and therapeutics for Parkinson’s disease. Neurotherapeutics 7(4):413–423CrossRefPubMedPubMedCentralGoogle Scholar
  50. Robertson RG, Graham WC, Sambrook MA, Crossman AR (1991) Further investigations into the pathophysiology of MPTP-induced parkinsonism in the primate: an intracerebral microdialysis study of gamma-aminobutyric acid in the lateral segment of the globus pallidus. Brain Res 563(1–2):278–280CrossRefPubMedGoogle Scholar
  51. Said SI (2000) The Viktor mutt memorial lecture. Protection by VİP and related peptides against cell death and tissue injury. Ann N Y Acad Sci 921:264–274CrossRefPubMedGoogle Scholar
  52. Sari Y, Gozes I (2006) Brain deficits associated with fetal alcohol exposure may be protected, in part, by peptides derived from activity-dependent neurotrophic factor and activity-dependent neuroprotective protein. Brain Res Rev 52(1):107–118CrossRefPubMedGoogle Scholar
  53. Segovia J, Tossman U, Herrera-Marschitz M, Garcia-Munoz M, Ungerstedt U (1986) Gamma-aminobutyric acid release in the globus pallidus in vivo after a 6-hydroxydopamine lesion in the substantia nigra of the rat. Neurosci Lett 70(3):364–368CrossRefPubMedGoogle Scholar
  54. Segovia J, Tillakaratne NJ, Whelan K, Tobin AJ, Gale K (1990) Parallel increases in striatal glutamic acid decarboxylase activity and mRNA levels in rats with lesions of the nigrostriatal pathway. Brain Res 529(1–2):345–348CrossRefPubMedGoogle Scholar
  55. Shimizu H, Watanabe E, Hiyama TY, et al. (2007) Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. Neuron 54(1):59–72CrossRefPubMedGoogle Scholar
  56. Sian J, Dexter DT, Lees AJ, et al. (1994) Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36(3):348–355CrossRefPubMedGoogle Scholar
  57. Soghomonian JJ, Laprade N (1997) Glutamate decarboxylase (GAD 67 and GAD 65) Gene expression is increased in a subpopulation of neurons in the putamen of parkinsonian monkeys. Synapse 27:122–132pCrossRefPubMedGoogle Scholar
  58. Stephens B, Mueller AJ, Shering AF, et al. (2005) Evidence of a breakdown of corticostriatal connections in Parkinson’s disease. Neuroscience 132(3):741–754CrossRefPubMedGoogle Scholar
  59. Takuma K, Baba A, Matsuda T (2004) Astrocyte apoptosis: implications for neuroprotection. Prog Neurobiol 72(2):111–127CrossRefPubMedGoogle Scholar
  60. Tarczyluk MA, Nagel DA, O’Neil JD (2013) Functional astrocyte-neuron lactate shuttle in a human stem cell-derived neuronal network. J Cereb Blood Flow Metab 33(9):1386–1393CrossRefPubMedPubMedCentralGoogle Scholar
  61. Toy D, Namgung UK (2013) Role of glial cells in axonal regeneration. Experimental Neurobiology 22(2):68–76CrossRefPubMedPubMedCentralGoogle Scholar
  62. Tunçel N, Sener E, Cerit C, et al. (2005) Brain mast cells and therapeutic potential of vasoactive intestinal peptide in a Parkinson’s disease model in rats: brain microdialysis, behavior, and microscopy. Peptides 26:827–836CrossRefPubMedGoogle Scholar
  63. Tunçel N, Korkmaz OT, Tekin N, Şener E, Akyüz F, Inal M (2012) Antioxidant and Antiapoptotic activity of vasoactive intestinal peptide (VİP) against 6 hydroxydopamine toxicity in the rat corpus striatum. J Mol Neurosci 46(1):51–57CrossRefPubMedGoogle Scholar
  64. Verkhratsky A, Olabarria M, Noristani HN, Yeh CY, Rodriguez JJ (2010) Astrocytes in Alzheimer’s disease. Neurotherapeutics 7(4):399–412CrossRefPubMedGoogle Scholar
  65. Yoon BE, Woo J, Lee CJ (2012) Astrocytes as GABA-ergic and GABA-ceptive cells. Neurochemical Research. 37:2474–2479CrossRefPubMedGoogle Scholar
  66. Zamostiano R, Pinhasov A, Gelber E, et al. (2001) Cloning and characterization of the human activity-dependent neuroprotective protein. J Biol Chem 276:708–714CrossRefPubMedGoogle Scholar
  67. Zupan V, Hill JM, Brenneman DE, et al. (1998) Involvement of pituitary adenylate cyclase-activating polypeptide II vasoactive intestinal peptide 2 receptor in mouse neocortical astrocytogenesis. J Neurochem 70:2165–2173CrossRefPubMedGoogle Scholar
  68. Zusev M, Gozes I (2004) Differential regulation of activity dependent neuroprotective protein in rat astrocytes by VİP and PACAP. Regul Pept 123:33–41CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • İbrahim Halil Yelkenli
    • 1
  • Emel Ulupinar
    • 2
  • Orhan Tansel Korkmaz
    • 1
  • Erol Şener
    • 3
  • Gökhan Kuş
    • 4
  • Zeynep Filiz
    • 5
  • Neşe Tunçel
    • 1
    Email author
  1. 1.Department of Physiology and Neurophysiology, Medical FacultyEskisehir Osmangazi UniversityEskişehirTurkey
  2. 2.Department of Anatomy, Medical FacultyEskisehir Osmangazi UniversityEskisehirTurkey
  3. 3.Department of Analytical Chemistry, Pharmacy FacultyAnadolu UniversityEskisehirTurkey
  4. 4.Department of Health Program, Open FacultyAnadolu UniversityEskisehirTurkey
  5. 5.Department of Statistics, Science and Art FacultyEskişehir Osmangazi UniversityEskisehirTurkey

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