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Transcriptome analysis of nicotine-exposed cells from the brainstem of neonate spontaneously hypertensive and Wistar Kyoto rats

The Pharmacogenomics Journal volume 10, pages 134–160 (2010)Cite this article

Abstract

In this study, the effects of nicotine on global gene expression of cultured cells from the brainstem of spontaneously hypertensive rat (SHR) and normotensive Wistar Kyoto (WKY) rats were evaluated using whole-genome oligoarrays. We found that nicotine may act differentially on the gene expression profiles of SHR and WKY. The influence of strain was present in 321 genes that were differentially expressed in SHR as compared with WKY brainstem cells independently of the nicotine treatment. A total of 146 genes had their expression altered in both strains after nicotine exposure. Interaction between nicotine treatment and the strain was observed to affect the expression of 229 genes that participate in cellular pathways related to neurotransmitter secretion, intracellular trafficking and cell communication, and are possibly involved in the phenotypic differentiation between SHR and WKY rats, including hypertension. Further characterization of their function in hypertension development is warranted.

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References

  1. Hallback M, Weiss L . Mechanisms of spontaneous hypertension in rats. Med Clin North Am 1977; 61: 593–609.

    Article  CAS  PubMed  Google Scholar 

  2. Ferrari MF, Fior-Chadi DR . Differential expression of nNOS mRNA and protein in the nucleus tractus solitarii of young and aged Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens 2005; 23: 1683–1690.

    Article  CAS  PubMed  Google Scholar 

  3. Mann SJ . Neurogenic essential hypertension revisited: the case for increased clinical and research attention. Am J Hypertens 2003; 16: 881–888.

    Article  PubMed  Google Scholar 

  4. Haass M, Kubler W . Nicotine and sympathetic neurotransmission. Cardiovasc Drugs Ther 1997; 10: 657–665.

    Article  CAS  PubMed  Google Scholar 

  5. Okamoto K, Tabei R, Yamori Y, Ooshima A . Spontaneously hypertensive rat as a useful model for hypertension research. Jikken Dobutsu 1973; 22 Suppl: 289–298.

    PubMed  Google Scholar 

  6. Dickhout JG, Lee RM . Blood pressure and heart rate development in young spontaneously hypertensive rats. Am J Physiol 1998; 274: H794–H800.

    CAS  PubMed  Google Scholar 

  7. Ferrari MFR, Fior-Chadi DR . Chronic nicotine administration. Analysis of the development of hypertension and glutamatergic neurotransmission. Brain Res Bull 2007; 72: 215–224.

    Article  CAS  PubMed  Google Scholar 

  8. Colombari E, Sato MA, Cravo SL, Bergamaschi CT, Campos Jr RR, Lopes OU . Role of the medulla oblongata in hypertension. Hypertension 2001; 38: 549–554.

    Article  CAS  PubMed  Google Scholar 

  9. Guyenet PG . The sympathetic control of blood pressure. Nat Rev Neurosci 2006; 7: 335–346.

    Article  CAS  PubMed  Google Scholar 

  10. Biscoe TJ, Sampson SR . Field potentials evoked in the brain stem of the cat by stimulation of the carotid sinus, glossopharyngeal, aortic and superior laryngeal nerves. J Physiol 1970; 209: 341–358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lipski J, McAllen RM, Spyer KM . The sinus nerve and baroreceptor input to the medulla of the cat. J Physiol 1975; 251: 61–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Blessing WW, Furness JB, Costa M, West MJ, Chalmers JP . Projection of ventrolateral medullary (A1) catecholamine neurons toward nucleus tractus solitarii. Cell Tissue Res 1981; 220: 27–40.

    Article  CAS  PubMed  Google Scholar 

  13. Kannan H, Yamashita H . Connections of neurons in the region of the nucleus tractus solitarius with the hypothalamic paraventricular nucleus: their possible involvement in neural control of the cardiovascular system in rats. Brain Res 1985; 329: 205–212.

    Article  CAS  PubMed  Google Scholar 

  14. Terreberry RR, Neafsey EJ . The rat medial frontal cortex projects directly to autonomic regions of the brainstem. Brain Res Bull 1987; 19: 639–649.

    Article  CAS  PubMed  Google Scholar 

  15. Guo ZL, Li P, Longhurst JC . Central pathways in the pons and midbrain involved in cardiac sympathoexcitatory reflexes in cats. Neuroscience 2002; 113: 435–447.

    Article  CAS  Google Scholar 

  16. Diz DI, Barnes KL, Ferrario CM . Hypotensive actions of microinjections of angiotensin II into the dorsal motor nucleus of the vagus. J Hypertens Suppl 1984; 2: S53–S56.

    CAS  PubMed  Google Scholar 

  17. Irmak MK, Sizlan A . Essential hypertension seems to result from melatonin-induced epigenetic modifications in area postrema. Med Hypotheses 2006; 66: 1000–1007.

    Article  CAS  PubMed  Google Scholar 

  18. Ferrari MF, Raizada MK, Fior-Chadi DR . Nicotine modulates the renin-angiotensin system of cultured neurons and glial cells from cardiovascular brain areas of Wistar Kyoto and spontaneously hypertensive rats. J Mol Neurosci 2007; 33: 284–293.

    Article  CAS  PubMed  Google Scholar 

  19. Russell VA . Dopamine hypofunction possibly results from a defect in glutamate-stimulated release of dopamine in the nucleus accumbens shell of a rat model for attention deficit hyperactivity disorder—the spontaneously hypertensive rat. Neurosci Biobehav Rev 2003; 27: 671–682.

    Article  CAS  PubMed  Google Scholar 

  20. Waki H, Murphy D, Yao ST, Kasparov S, Paton JF . Endothelial NO synthase activity in nucleus tractus solitarii contributes to hypertension in spontaneously hypertensive rats. Hypertension 2006; 48: 644–650.

    Article  CAS  PubMed  Google Scholar 

  21. Carrettiero DC, Fior-Chadi DR . Adenosine A1 receptor distribution in the nucleus tractus solitarii of normotensive and spontaneously hypertensive rats. J Neural Transm 2004; 111: 465–473.

    Article  CAS  PubMed  Google Scholar 

  22. Lee TS, Mane S, Eid T, Zhao H, Lin A, Guan Z et al. Gene expression in temporal lobe epilepsy is consistent with increased release of glutamate by astrocytes. Mol Med 2007; 13: 1–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Aston C, Jiang L, Sokolov BP . Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res 2004; 77: 858–866.

    Article  CAS  PubMed  Google Scholar 

  24. Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW . Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA 2004; 101: 2173–2178.

    Article  CAS  PubMed  Google Scholar 

  25. Kivell BM, McDonald FJ, Miller JH . Method for serum-free culture of late fetal and early postnatal rat brainstem neurons. Brain Res Brain Res Protoc 2001; 6: 91–99.

    Article  CAS  PubMed  Google Scholar 

  26. Bolstad BM, Irizarry RA, Astrand M, Speed TP . A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 2003; 19: 185–193.

    Article  CAS  PubMed  Google Scholar 

  27. Eisen MB, Spellman PT, Brown PO, Botstein D . Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 1998; 95: 14863–14868.

    Article  CAS  PubMed  Google Scholar 

  28. Hosack DA, Dennis Jr G, Sherman BT, Lane HC, Lempicki RA . Identifying biological themes within lists of genes with EASE. Genome Biol 2003; 4: R70.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 2001; 25: 402–408.

    Article  CAS  Google Scholar 

  30. Wang J, Gutala R, Hwang YY, Kim JM, Konu O, Ma JZ et al. Strain- and region-specific gene expression profiles in mouse brain in response to chronic nicotine treatment. Genes Brain Behav 2008; 7: 78–87.

    PubMed  Google Scholar 

  31. Dunckley T, Lukas RJ . Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. J Biol Chem 2003; 278: 15633–15640.

    Article  CAS  PubMed  Google Scholar 

  32. Thibault C, Hassan S, Miles M . Using in vitro models for expression profiling studies on ethanol and drugs of abuse. Addict Biol 2005; 10: 53–62.

    Article  CAS  PubMed  Google Scholar 

  33. Ferrari MF, Reis EM, Matsumoto JP, Fior-Chadi DR . Gene expression profiling of cultured cells from brainstem of newborn spontaneously hypertensive and Wistar Kyoto rats. Cell Mol Neurobiol 2009; 29: 287–308.

    Article  CAS  PubMed  Google Scholar 

  34. Xu Y, Krukoff TL . Adrenomedullin in the rostral ventrolateral medulla inhibits baroreflex control of heart rate: a role for protein kinase A. Br J Pharmacol 2006; 148: 70–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cui H, Kohsaka A, Waki H, Gouraud S, Nakamura T, Yukawa K et al. Adrenomedullin 2 microinjection into the nucleus tractus solitarius elevates arterial pressure and heart rate in rats. Auton Neurosci 2008; 142: 45–50.

    Article  CAS  PubMed  Google Scholar 

  36. Patel JV, Lim HS, Varughese GI, Hughes EA, Lip GY . Angiopoietin-2 levels as a biomarker of cardiovascular risk in patients with hypertension. Ann Med 2008; 40: 215–222.

    Article  CAS  PubMed  Google Scholar 

  37. Sun Y, Jin K, Childs JT, Xie L, Mao XO, Greenberg DA . Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: evidence from knockout mice and growth factor administration. Dev Biol 2006; 289: 329–335.

    Article  CAS  PubMed  Google Scholar 

  38. Manunta P, Citterio L, Lanzani C, Ferrandi M . Adducin polymorphisms and the treatment of hypertension. Pharmacogenomics 2007; 8: 465–472.

    Article  CAS  PubMed  Google Scholar 

  39. Feng J, Chi P, Blanpied TA, Xu Y, Magarinos AM, Ferreira A et al. Regulation of neurotransmitter release by synapsin III. J Neurosci 2002; 22: 4372–4380.

    Article  CAS  PubMed  Google Scholar 

  40. Pieribone VA, Porton B, Rendon B, Feng J, Greengard P, Kao HT . Expression of synapsin III in nerve terminals and neurogenic regions of the adult brain. J Comp Neurol 2002; 454: 105–114.

    Article  CAS  PubMed  Google Scholar 

  41. Ferreira A, Rapoport M . The synapsins: beyond the regulation of neurotransmitter release. Cell Mol Life Sci 2002; 59: 589–595.

    Article  CAS  PubMed  Google Scholar 

  42. Ferreira A, Kao HT, Feng J, Rapoport M, Greengard P . Synapsin III: developmental expression, subcellular localization, and role in axon formation. J Neurosci 2000; 20: 3736–3744.

    Article  CAS  PubMed  Google Scholar 

  43. Porton B, Wetsel WC . Reduction of synapsin III in the prefrontal cortex of individuals with schizophrenia. Schizophr Res 2007; 94: 366–370.

    Article  PubMed  Google Scholar 

  44. Firestone JA, Browning MD . Synapsin II phosphorylation and catecholamine release in bovine adrenal chromaffin cells: additive effects of histamine and nicotine. J Neurochem 1992; 58: 441–447.

    Article  CAS  PubMed  Google Scholar 

  45. Noakes PG, Chin D, Kim SS, Liang S, Phillips WD . Expression and localisation of dynamin and syntaxin during neural development and neuromuscular synapse formation. J Comp Neurol 1999; 410: 531–540.

    Article  CAS  PubMed  Google Scholar 

  46. Gray NW, Fourgeaud L, Huang B, Chen J, Cao H, Oswald BJ et al. Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer. Curr Biol 2003; 13: 510–515.

    Article  CAS  PubMed  Google Scholar 

  47. Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A et al. The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors. Mol Cell Neurosci 2001; 18: 13–25.

    Article  CAS  Google Scholar 

  48. McClure SJ, Robinson PJ . Dynamin, endocytosis and intracellular signalling (review). Mol Membr Biol 1996; 13: 189–215.

    Article  CAS  PubMed  Google Scholar 

  49. McPherson PS, Kay BK, Hussain NK . Signaling on the endocytic pathway. Traffic 2001; 2: 375–384.

    Article  CAS  PubMed  Google Scholar 

  50. Nakamura N, Miyake Y, Matsushita M, Tanaka S, Inoue H, Kanazawa H . KIF1Bbeta2, capable of interacting with CHP, is localized to synaptic vesicles. J Biochem 2002; 132: 483–491.

    Article  CAS  PubMed  Google Scholar 

  51. Szolnoki Z, Kondacs A, Mandi Y, Somogyvari F . A genetic variant in cytoskeleton motors amplifies susceptibility to leukoaraiosis in hypertensive smokers: gene-environmental interactions behind vascular white matter demyelinization. J Mol Neurosci 2007; 33: 173–179.

    Article  CAS  PubMed  Google Scholar 

  52. Cen X, Nitta A, Ibi D, Zhao Y, Niwa M, Taguchi K et al. Identification of Piccolo as a regulator of behavioral plasticity and dopamine transporter internalization. Mol Psychiatry 2008; 13: 349, 451–463.

    Article  CAS  PubMed  Google Scholar 

  53. Gerber SH, Garcia J, Rizo J, Sudhof TC . An unusual C(2)-domain in the active-zone protein piccolo: implications for Ca(2+) regulation of neurotransmitter release. EMBO J 2001; 20: 1605–1619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Menezes RC, Fontes MA . Cardiovascular effects produced by activation of GABA receptors in the rostral ventrolateral medulla of conscious rats. Neuroscience 2007; 144: 336–343.

    Article  CAS  PubMed  Google Scholar 

  55. Suzuki M, Kuramochi T, Suga T . GABA receptor subtypes involved in the neuronal mechanisms of baroreceptor reflex in the nucleus tractus solitarii of rabbits. J Auton Nerv Syst 1993; 43: 27–35.

    Article  CAS  PubMed  Google Scholar 

  56. Yao F, Sumners C, O’Rourke ST, Sun C . Angiotensin II increases GABAB receptor expression in nucleus tractus solitarii of rats. Am J Physiol Heart Circ Physiol 2008; 294: H2712–H2720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Couve A, Restituito S, Brandon JM, Charles KJ, Bawagan H, Freeman KB et al. Marlin-1, a novel RNA-binding protein associates with GABA receptors. J Biol Chem 2004; 279: 13934–13943.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by research grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq). JPPM received a mastering fellowship from CAPES (Ministry of Education). MFRF received a post-doctoral fellowship from FAPESP (06/00650-1).

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Authors and Affiliations

  1. Departamento de Neurologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil

    M F R Ferrari

  2. Departamento de Bioquímica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, SP, Brazil

    E M Reis

  3. Departamento de Fisiologia, Instituto de Biociencias, Universidade de Sao Paulo, Sao Paulo, SP, Brazil

    J P P Matsumoto & D R Fior-Chadi

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  1. M F R Ferrari
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Correspondence to M F R Ferrari.

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Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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Ferrari, M., Reis, E., Matsumoto, J. et al. Transcriptome analysis of nicotine-exposed cells from the brainstem of neonate spontaneously hypertensive and Wistar Kyoto rats. Pharmacogenomics J 10, 134–160 (2010). https://doi.org/10.1038/tpj.2009.42

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