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Regional Distribution and Relative Abundance of Serotonin2c Receptors in Human Brain: Effect of Suicide

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Abstract

Abnormalities in serotonin receptor subtypes have been observed in the postmortem brain of suicide victims. We examined the regional distribution of serotonin (5HT)2C receptor mRNA in several areas of the human brain and also compared its protein and mRNA expression in the prefrontal cortex (PFC), hippocampus, and choroid plexus between suicide victims and normal control subjects. 5HT2C receptors were found to be distributed in several areas of the human brain (in order of abundance): highly concentrated and richest in choroid plexus; hypothalamus; nucleus accumbens; with the lowest abundance in PFC and cerebellum. Comparison of 5HT2C receptors between suicide victims and control subjects showed higher protein levels in the PFC but not the hippocampus or choroid plexus of suicide victims. However, there were no significant differences in mRNA levels between suicide victims and control subjects in these brain areas. These results suggest that 5HT2C receptors are richly distributed throughout the brain with the highest level in the choroid plexus and that abnormalities in protein expression of 5HT2C receptors in the PFC may be associated with suicide.

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References

  1. Mann JJ, Arango V, Marzuk PM, Theccanat S, Reis DJ (1989) Evidence for the 5HT hypothesis of suicide. A review of postmortem studies. Br J Psych 155 suppl: 7–14

    Google Scholar 

  2. Ashberg M, Traskman L, Thoren P, (1976) 5HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psych 33:1193–1197

    Google Scholar 

  3. Traskman L, Asberg M, Bertilsson L, Sjostrand L (1981) Monoamine metabolites in CSF and suicidal behavior. Arch Gen Psych 38:631–636

    CAS  Google Scholar 

  4. Lidberg L, Belfrage H, Bertilsson L, Evenden MM, Asberg M (2000) Suicide attempts and impulse control disorder are related to low cerebrospinal fluid 5HIAA in mentally disordered violent offenders. Acta Psych Scand 101:395–402

    Article  CAS  Google Scholar 

  5. Spreux-Varoquaux O, Alvarez JC, Berlin I, Batista G, Despierre PG, Gilton A, Cremniter D (2001) Differential abnormalities in plasma 5HIAA and platelet serotonin concentrations in violent suicide attempters: relationships with impulsivity and depression. Life Sci 69:647–657

    Article  PubMed  CAS  Google Scholar 

  6. Barnes NM, Sharp T (1999) A review of central 5HT receptors and their function. Neuropharmacology 38:1083–1152

    Article  PubMed  CAS  Google Scholar 

  7. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PA (1994) VII. International Union of Pharmacology classification of receptor for 5-hydroxytrytamine (serotonin). Pharmacol Rev 46:157–203

    PubMed  CAS  Google Scholar 

  8. Hoyer D, Martin G (1997) 5HT receptor classification and nomenclature: towards a harmonization with the human genome. Neuropharmacology 36:419–428

    Article  PubMed  CAS  Google Scholar 

  9. Gross-Isseroff R, Biegon A, Voet H, Weizman A (1998) The suicide brain: a review of postmortem receptor/transporter binding studies. Neurosci Biobehav 22:653–661

    Article  CAS  Google Scholar 

  10. Stockmeier CA (2003) Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psych Res 37:357–373

    Article  Google Scholar 

  11. Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Pandey SC, Pesold C, Roberts RC, Conley RR, Tamminga CA (2002) Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims. Am J Psych 159:419–429

    Article  Google Scholar 

  12. Pazos A, Hoyer D, Palacios JM, (1984) The binding of serotonergic ligands to the porcine choroid plexus: characterization of a new type of serotonin recognition site. Eur J Pharmacol 106:539–546

    Article  PubMed  CAS  Google Scholar 

  13. Julius D, Huang KN, Livelli TJ, Axel R, Jessell TM, (1990) The 5HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors. Proc Natl Acad Sci USA 87:928–932

    Article  PubMed  CAS  Google Scholar 

  14. Higgins GA, Fletcher PJ, (2003) Serotonin and drug reward: focus on 5HT2C receptors. Eur J Pharmacol 480:151–162

    Article  PubMed  CAS  Google Scholar 

  15. Soubrie P (1986) Reconciling the role of central serotonin neurons in human and animal behaviour. Behav Brain Sci 9:319–364

    Google Scholar 

  16. Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB (1997) Regulation of serotonin2C receptor G-protein coupling by RNA editing. Nature 387:303–308

    Article  PubMed  CAS  Google Scholar 

  17. Gurevich I, Tamir H, Arango V, Dwork AJ, Mann JJ, Schmauss C (2002) Altered editing of serotonin2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron 34:349–356

    Article  PubMed  CAS  Google Scholar 

  18. Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E (2001) RNA editing of the human serotonin 5-HT2C receptor. Alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharmacology 24:478–491

    Article  PubMed  CAS  Google Scholar 

  19. Iwamoto K, Kato T (2003) RNA editing of serotonin2C receptor in human postmortem brains of major mental disorders. Neurosci Lett 346:169–172

    Article  PubMed  CAS  Google Scholar 

  20. Schmauss C (2003) Serotonin2C receptors: suicide, serotonin, and runaway RNA editing. Neuroscientist 9:237–242

    Article  PubMed  CAS  Google Scholar 

  21. Niswender CM, Copeland SC, Herrick-Davis K, Emeson RB, Sanders-Bush E (1999) RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J Biol Chem 274:9472–9478

    Article  PubMed  CAS  Google Scholar 

  22. Marazziti D, Rossi A, Giannaccini G, Zavaglia KM, Dell’Osso L, Lucacchini A, Cassano GB (1999) Distribution and characterization of [3H]mesulergine binding in human brain postmortem. Eur Neuropsychopharmacol 10:21–26

    Article  PubMed  CAS  Google Scholar 

  23. Pasqualetti M, Ori M, Castagna M, Marazziti D, Cassano GB, Nardi I (1999) Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain. Neuroscience 92:601–611

    Article  PubMed  CAS  Google Scholar 

  24. Lopez-Gimenez JF, Mengod G, Palacios JM, Vilaro MT (2001) Regional distribution and cellular localization of 5HT2C receptor mRNA in monkey brain: comparison with [3H]mesulergine binding sites and choline acetyltransferase mRNA. Synapse 42:12–26

    Article  PubMed  CAS  Google Scholar 

  25. Spitzer RL, Williams JBW, Gibbon M, First MB (1995) Structured Clinical Interview for DSM-IV (SCID). New York State Psychiatric Institute, Biometrics Research, New York

    Google Scholar 

  26. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2002) mRNA and protein expression of selective alpha subunits of G proteins are abnormal in prefrontal cortex of suicide victims. Neuropsychopharmacology 27:499–517

    PubMed  CAS  Google Scholar 

  27. Dwivedi Y, Rizavi HS, Shukla PK, Lyons J, Faludi G, Palkovits M, Sarosi A, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2004) Protein kinase A in postmortem brain of depressed suicide victims: altered expression of specific regulatory and catalytic subunits. Biol Psych 55:234–243

    Article  CAS  Google Scholar 

  28. Giorgetti M, Tecott LH (2004) Contributions of 5HT2C receptors to multiple actions of central serotonin systems. Eur J Pharmacol 488:1–9

    Article  PubMed  CAS  Google Scholar 

  29. Tecott LH, Sun LM Akana SF, Strack AM, Lowenstein DH, Dallman MF, Julius D (1995) Eating disorders and epilepsy in mice lacking 5HT2C serotonin receptors. Nature 374:542–546

    Article  PubMed  CAS  Google Scholar 

  30. Fitzgerald LW, Iyer G, Conklin DS, Krause CM, Marshall A, Patterson JP, Tran DP, Jonak GJ (1999) Messenger RNA editing of the human serotonin 5HT2C receptor. Neuropsychopharmacology 21:825–905

    Google Scholar 

  31. Gurevich I, Englander MT, Adlersberg M, Siegal NB, Schmauss C (2002) Modulation of serotonin2C receptor editing by sustained changes in serotonergic neurotransmission. J Neurosci 22:10529–10532

    PubMed  CAS  Google Scholar 

  32. Sodhi MS, Burnet PWJ, Makoff AJ, Kerwin RW, Harrison PJ (2001) RNA editing of the 5-HT2C receptor is reduced in schizophrenia. Mol Psych 6:373–379

    Article  CAS  Google Scholar 

  33. Castensson A, Emilsson L, Sundberg R, Jazin E (2003) Decrease of serotonin receptor2C in schizophrenia brains identified by high-resolution mRNA expression analysis. Biol. Psych 54:1212–1221

    Article  CAS  Google Scholar 

  34. Yang W, Wang Q, Kanes SJ, Murray JM, Nishikura K (2004) Altered RNA editing of serotonin 5HT2C receptor induced by interferon: implications for depression associated with cytokine therapy. Brain Res Mol Brain Res 124:70–78

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants RO1 MH 48153 (Dr. Pandey) and KO1 MH 01836 and RO1 MH 068777 (Dr. Dwivedi) from the National Institute of Mental Health, Rockville, MD; and from the American Foundation for Suicide Prevention (Dr. Dwivedi), New York, NY and MTA/TKI, Budapest, Hungary. We thank Barbara Brown, Miljana Petkovic, and Magdolna Kasztner for their help in organizing the brain tissue.

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Authors and Affiliations

  1. The Psychiatric Institute, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL, 60612, USA

    Ghanshyam N. Pandey, Yogesh Dwivedi, Xinguo Ren & Hooriyah S. Rizavi

  2. Department of Psychiatry, Semmelweis University, Kútvölgyi Clinical Center, Budapest, Hungary

    Gabor Faludi & Andrea Sarosi

  3. Laboratory of Neuromorphology, Semmelweis University and the Hungarian Academy of Sciences, Budapest, Hungary

    Miklos Palkovits

  4. The Psychiatric Institute, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL, 60612, USA

    Ghanshyam N. Pandey

Authors
  1. Ghanshyam N. Pandey
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  2. Yogesh Dwivedi
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  3. Xinguo Ren
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  4. Hooriyah S. Rizavi
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  5. Gabor Faludi
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  6. Andrea Sarosi
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  7. Miklos Palkovits
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Correspondence to Ghanshyam N. Pandey.

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Special Issue Dedicated to Miklós Palkovits

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Pandey, G.N., Dwivedi, Y., Ren, X. et al. Regional Distribution and Relative Abundance of Serotonin2c Receptors in Human Brain: Effect of Suicide. Neurochem Res 31, 167–176 (2006). https://doi.org/10.1007/PL00022053

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