Skip to main content
Log in

The Effect of Citalopram on Gene Expression Profile of Alzheimer Lymphocytes

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Antidepressants are widely used in the treatment of mood disorders associated with dementia, however little information is available on their effect at the molecular level. In certain neurodegenerative disorders, such as in Alzheimer's disease, lymphocytes have been used to assess mirror changes that thought to occur in the brain. Gene expression profiles of lymphocytes from Alzheimer patients have been shown to differ from that seen with controls. To address this issue in light of antidepressant treatment, we used lymphocytes derived from Alzheimer's disease patients and control individuals to assess the impact of the selective serotonine reuptake inhibitor citalopram on gene expression using a cDNA microarray representing 3200 distinct human genes. Sequences that are differentially regulated after treatment with citalopram were identified and categorized based on similarities in biological functions. This analysis revealed that the overexpression of genes in control and Alzheimer white blood cells by citalopram are implicated in cell survival. Apart from this, citalopram did not markedly alter genes involved in other molecular functions in control cells. In contrast, alteration of genes implicated in ionic currents, cell-adhesion, immune mechanism, and adrenergic functions, were also observed in Alzheimer lymphocytes. The expression of genes of Alzheimer lymphocytes by citalopram is modulated differently which may correlate with the pathology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

references

  1. Selkoe, D. J. The molecular pathology of Alzheimer's disease. 1991. Neuron 6:487–498.

    Google Scholar 

  2. Terry, R. D. Neuropathological changes in Alzheimer disease. 1994. Prog. Brain Res. 101:383–390.

    Google Scholar 

  3. Lyketsos, C. G., Steinberg, M., Tschantz, J., Norton, M., Steffens, D., and Breitner, J. C. S. 2000. Mental and behavioral disturbances in dementia: Findings from the Cache County Study on Memory in Aging. Am. J. Psychiatry 157:708–714.

    Google Scholar 

  4. Olin, J. T., Schneider, L. S., Katz, I. R., Meyers, B. S., Alexopoulos, G. S., Breitner, J. C., Bruce, M. L., Caine, E. D., Cummings, J. L., Devanand, D. P., Krishnan, K. R., Lyketsos, C. G., Lyness, J. M., Rabins, P. V., Reynolds, C. F. 3rd, Rovner, B. W., Steffens, D. C., Tariot, P. N., and Lebowitz, B. D. 2002. Provisional diagnostic criteria for depression of Alzheimer disease. Am. J. Geriatr. Psychiatry 10:125–128.

    Google Scholar 

  5. Duman, R. S., Heninger, G. R., and Nestler, E. I. 1997. A molecular and cellular theory of depression. Arch. Gen. Psychiatry 54:597–606.

    Google Scholar 

  6. Berger, B. Neurotransmitter anomalies in Alzheimer's disease. 1984. Rev. Neurol. 10:539–552.

    Google Scholar 

  7. Bowen, D. M., Allen, S. J., Benton, J. S., Goodhardt, M. J., Haan, E. A., Palmer, A. M., Sims, N. R., Smith, C. C., Spillane, J. A., Esiri, M. M., Neary, D., Snowdo, J. S., Wilcock, G. K., Davison, A. N. 1983. Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease. J. Neurochem. 41:266–272.

    Google Scholar 

  8. Palotás, M., Palotás, A., Puskás, L. G., Kitajka, K., Pákáski, M., Janka, Z., Molnár, J., Penke, B., and Kálmán, J. 2004. Gene expression profile analysis of the rat cortex following treatment with imipramine and citalopram. Int. J. Neuropsychopharm. (in press).

  9. Palotás A., Kálmán, J., Laskay, G., Juhász, A., Janka, Z., and Penke, B. 2001. Comparative studies on [Ca2+]i-level of fibroblasts from Alzheimer patients and control individuals. Neurochem. Res. 26:817–820.

    Google Scholar 

  10. Zubenko, G. S., Cohen, B. M., Growdon, J., and Corkin, S. 1984. Cell membrane abnormality in Alzheimer's disease. Lancet 2:235.

    Google Scholar 

  11. Kálmán, J., Dey, I., Ilona, S. V., Matkovics, B., Brown, D., Janka, Z., Farkas, T., and Joó, F. 1994. Platelet membrane fluidity and plasma malondialdehyde levels in Alzheimer's demented patients with and without family history of dementia. Biol. Psychiat. 35:190–194.

    Google Scholar 

  12. Zubenko, G. S. 1989. Endoplasmic reticulum abnormality in Alzheimer's disease: selective alteration in platelet NADH-cytochrome C reductase activity. J. Geriatr. Psychiat. Neurol. 2:3–10.

    Google Scholar 

  13. Di Luca, M., Pastorino, L., Bianchetti, A., Perez, J., Vignolo, L. A., Lenzi, G. L., Trabucchi, M., Cattabeni, F., and Padovani, A. 1988. Differential level of platelet amyloid beta precursor protein isoforms: an early markers for Alzheimer's disease. Arch. Neurol. 55:1195–1200.

    Google Scholar 

  14. Perry, R. H., Wilson, I. D., Bober, M. J., Atack, J., Blessed, G., Tomlinson, B. E., and Perry, E. K. 1982. Plasma and erythrocyte acetylcholinesterase in senile dementia of Alzheimer type. Lancet 1:174–175.

    Google Scholar 

  15. Palotás, A., Kálmán, J., Palotás, M., Juhász, A., Janka, Z., and Penke, B. 2002. β-amyloid induced increase in the resting intracellular calcium concentration gives support to tell Alzheimer lymphocytes from control ones. Brain Res. Bull. 58:203–205.

    Google Scholar 

  16. Etcheberrigaray, R. and Bhagavan, S. Ionic and signal transduction alterations in Alzheimer's disease: Relevance of studies on peripheral cells. 1999. Mol. Neurobiol. 20:93–109.

    Google Scholar 

  17. Eckert, A., Cotman, C. W., Zerfass, R., Hennerici, M., and Muller, W. E. Lymphocytes as cell model to study apoptosis in Alzheimer's disease: vulnerability to programmed cell death appears to be altered. 1998. J. Neurol. Transm. Suppl. 54:259–267.

    Google Scholar 

  18. Bergman, M., Salman, H., Beloosesky, Y., Djaldetti, M., and Bessler, H. 2002. Are peripheral blood cells from patients with Alzheimer's disease more sensitive to apoptotic stimuli? Alzheimer Dis. Assoc. Dis. 16:156–160.

    Google Scholar 

  19. Mórocz, M., Kálmán, J., Juhász, A., Sinkó, I., McGlynn, A. P., Downes, C. S., Janka, Z., Raskó, I. 2002. Elevated levels of oxidative DNA damage in lymphocytes from patients with Alzheimer's disease. Neurobiol. Aging 23:47–53.

    Google Scholar 

  20. Dolman, C. L. 1984. Diagnosis of neurometabolic disorders by examination of skin biopsies and lymphocytes. Semin. Diagn. Pathol. 1:82–97.

    Google Scholar 

  21. Kálmán, J., Kitajka, K., Pákáski, M., Zvara, Á., Juhász, A., Vincze, G., Janka, Z., and Puskás, L. G. 2004. Gene expression profile analysis of lymphocytes from Alzheimer's patients. (in press)

  22. Kitajka, K., Puskás, L. G., Zvara, Á., Hackler, L. Jr., Barcelo-Coblijn, G., Yeo Y. K., and Farkas T. 2002. The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc. Natl. Acad. Sci. USA 99:2619–2624.

    Google Scholar 

  23. Puskás, L. G., Hackler, L. Jr., Kovács, G., Kupihár, Z., Zvara Á., Micsik, T., and van Hummelen P. 2002. Recovery of cyanine-dye nucleotide triphosphates. Anal. Biochem. 305:279–281.

    Google Scholar 

  24. Puskás, L. G., Zvara Á, Hackler, L. J., and van Hummelen, P. 2002. Comparison of different sample amplification method for microarray gene expression analysis. RNA amplification results in reproducible microarray data with slight ratio bias. Biotechniques 32:1330–1340.

    Google Scholar 

  25. Herwig, S., and Strauss, M. 1997. The retinoblastoma protein: a master regulator of cell cycle, differentiation and apoptosis. Eur. J. Biochem. 246:581–601.

    Google Scholar 

  26. Rohn, T. T., Head, E., Su, J. H., Anderson, A. J., Bahr, B. A., Cotman, C. W., and Cribbs, D. H. 2001. Correlation between caspase activation and neurofibrillary tangle formation in Alzheimer's disease. Am. J. Pathol. 158:189–198.

    Google Scholar 

  27. Takeda, M., Tatebayashi, Y., and Nishimura, T. 1992. Change in the cytoskeletal system in fibroblasts from patients with familial Alzheimer's disease. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 16:317–328.

    Google Scholar 

  28. Tollefson, G. D., Godes, M., Warren, J. B., Haus, E., Luxenberg, M., and Garvey, M. 1989. Lymphopenia in primary degenerative dementia. J. Psychiatr. Res. 23:191–199.

    Google Scholar 

  29. Serafeim, A. and Gordon, J. 2001. The immune system gets nervous. Curr. Opin. Pharmacol. 1:398–403.

    Google Scholar 

  30. Nagga, A. K. and Marcusson, J. 1998. Associated physical disease in a demented population. Aging Milano 10:440–444.

    Google Scholar 

  31. McGeer, P. L. and McGeer, E. G. 2002. The possible role of complement activation in Alzheimer's disease. Trends Mol. Med. 8:519–523.

    Google Scholar 

  32. Mossner, R. and Lesch, K. P. 1998. Role of serotonin in the immune system and in neuroimmune interactions. Brain Behav. Immun. 12:249–271.

    Google Scholar 

  33. Stefulj J., Jernej, B., Cicin-Sain, L., Rinner, I., and Schauenstein, K. mRNA expression of serotonin receptors in cells of the immune tissues of the rat. 2000. Brain Behav. Immun. 14:219–224.

    Google Scholar 

  34. Aune, T. M., Kelley, K. A., Ranges, G. E., Bombara, M. P., 1990. Serotonin-activated signal transduction via serotonin receptors on Jurkat cells. J. Immunol. 145:1826–1832.

    Google Scholar 

  35. Plaut, M. Lymphocyte hormone receptors. 1987. Ann. Rev. Immunol. 5:621–629.

    Google Scholar 

  36. Hellstrand, K. and Hermodsson, S., Role of serotonin in the regulation of human natural killer cell cytotoxicity, 1987. J. Immunol. 139:869–875.

    Google Scholar 

  37. Bonnet, M., Lespinats, G., and Burtin, C. Histamine and serotonin suppression of lymphocyte response to phytohemagglutinin and allogenic cells. 1984. Cell. Immunol. 83:280–291.

    Google Scholar 

  38. Bellinger, D. L., Felten, S. Y., and Felten, D. L. 1988. Maintenance of non-adrenergic sympathetic innervation in the involuted thymus of the aged Fisher 344 rat. Brain Behav. Immunol. 2:133–150.

    Google Scholar 

  39. Hershey, J. W. B. and Merrick, W. C. 2000. Pathway and mechanism of initiation of protein synthesis. Pages 33–88, in Sonenberg N., Hershey, J. W. B., Mathews, M. B., eds. Translational control of gene expression, (2nd Ed.), Cold Spring Harbor: Cold Spring Harbor Laboratory Press.

    Google Scholar 

  40. Schauenstein, K., Felsner, P., Rinner, I., Liebmann, P. M., Stevenson, J. R., Westermann, J., Haas, H. S., Cohen, R. L., and Chambers, D. A. 2000. In vivo immunomodulation by peripheral adrenergic and cholinergic agonists/antagonists in rat and mouse models. Ann. N. Y. Acad. Sci. 917:618–627.

    Google Scholar 

  41. Rabey, J. M., Shenkman, L., Gilad, G. M. 1986. Cholinergic muscarinic binding by human lymphocytes: change with aging, antagonist treatment, and senile dementia of the Alzheimer type. Ann. Neurol. 20:628–631.

    Google Scholar 

  42. Amenta, F., Bronzetti, E., Fellici, L., Ricci, A., Tayebati, S. K., 1999. Dopamine D2-like receptors on human peripheral blood lymphocytes: a radioligand binding assay and immunocytochemical study. J. Auton. Pharmacol. 19:151–159.

    Google Scholar 

  43. Nagai, Y., Ueno, S., Saeki, Y., Soga, F., and Yanagihara, T. 1993. Expression of the D3 dopamine receptor gene and a novel variant transcript generated by alternative splicing in human peripheral blood lymphocytes. Biochem. Biophys. Res. Commun. 194:374–386.

    Google Scholar 

  44. Ricci, A., Bronzetti, E., Felici, L., Tayebati, S. K., and Amenta, F., 1997. Dopamine D4 receptor in human peripheral blood lymphocytes: a radioligand binding assay study. Neurosci. Lett. 229:130–134.

    Google Scholar 

  45. Takahashi, N., Nagai, Y., Ueno, S., Saeki, Y., and Yanagihara, T. 1992. Human peripheral blood lymphocytes express D5 dopamine receptor gene and transcribe the two pseudogenes. FEBS Lett. 314:23–25.

    Google Scholar 

  46. Rocca, P., Ferrero, P., Gualerzi, A., Zanalda, E., Maina, G., Bergamasco, B., and Ravizza, L. 1991. Peripheral type of benzodiazepine receptors in anxiety disorders. Acta Psychiatr. Scand. 84:537–544.

    Google Scholar 

  47. Stanisz, A. N., Scicchitano, R., Dazin, P., Bienenstock, J., and Payan, D. G. 1987. Distribution of substance P receptors on murine spleen and Peyer's patch T and B cells. J. Immunol. 139:749–756.

    Google Scholar 

  48. Evans, C. J., Erdélyi, E., Barchas, J. D. 1986. Candidate opioid peptides for the interaction with the immune system. Pages 3–16, in Plotnikoff, N. P., Faith, R. E., Murgo, A. J. and Goog, A., (eds.), Enkephalins and endorphins, Plenum, New York.

    Google Scholar 

  49. Viik, P., Opstad, P. K., and Boyum A. Binding of vasoactive intestinal polypeptide (VIP) by human monocytes: demonstration of specific binding sites. 1985. Regul. Pept. 12:145–153.

    Google Scholar 

  50. Bishopric, N. H., Cohen, H. J., and Lefkowitz, R. J. β-adrenergic receptors in lymphocyte subpopulations. 1980. J. Allergy Clin. Immunol. 63:29–33.

    Google Scholar 

  51. Shenkman, L., Rabey, J. M., Gilad, G. M. Cholinergic muscarinic binding by rat lymphocytes: effects of antagonist treatment, strain and aging. 1991. Brain Res. 564:203–219.

    Google Scholar 

  52. D'Amato, R. J., Zweig, R. M., Whitehouse, P. J., Wenk, G. L., Singer, H. S., Mayeux, R., Price, D. L., and Snyder, S. H. 1987. Aminergic systems in Alzheimer's disease and Parkinson's disease. Ann. Neurol. 22:229–236.

    Google Scholar 

  53. Zweig, R. M., Ross, C. A., Hedreen, J. C., Steele, C., Cardillo, J. E., Whitehouse, P. J., Folstein, M. F., Price, D. L. 1988. The neuropathology of aminergic nuclei in Alzheimer's disease. Ann. Neurol. 24:233–242.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to András Palotás.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Palotás, A., Puskás, L.G., Kitajka, K. et al. The Effect of Citalopram on Gene Expression Profile of Alzheimer Lymphocytes. Neurochem Res 29, 1563–1570 (2004). https://doi.org/10.1023/B:NERE.0000029570.57903.74

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NERE.0000029570.57903.74

Navigation