Disease-specific expression of the serotonin-receptor 5-HT2C in natural killer cells in Alzheimer's dementia

Luiza Conceição Amorim Martins, Natália Pessoa Rocha, Karen Cecília Lima Torres, Rodrigo Ribeiro dos Santos, Giselle Sabrina França, Edgar Nunes de Moraes, Marat Alexandrovich Mukhamedyarov, Andrey Lvovich Zefirov, Albert Anatolyevich Rizvanov, Andrey Pavlovich Kiyasov, Luciene Bruno Vieira, Melissa Monteiro Guimarães, Mehmet Emir Yalvaç, Antônio Lúcio Teixeira, Maria Aparecida Camargo Bicalho, Zoltán Janka, Marco Aurélio Romano-Silva, András Palotás, Helton José Reis

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20 Citations (Scopus)

Abstract

Alzheimer's dementia (AD) is a degenerative brain disorder characterized mainly by cholinergic failure, but other neuro-transmitters are also deficient especially at late stages of the disease. Misfolded β-amyloid peptide has been identified as a causative agent, however inflammatory changes also play a pivotal role. Even though the most prominent pathology is seen in the cognitive functions, specific abnormalities of the central nervous system (CNS) are also reflected in the periphery, particularly in the immune responses of the body. The aim of this study was to characterize the dopaminergic and serotonergic systems in AD, which are also markedly disrupted along with the hallmark acetyl-choline dysfunction. Peripheral blood mono-nuclear cells (PBMCs) from demented patients were judged against comparison groups including individuals with late-onset depression (LOD), as well as non-demented and non-depressed subjects. Cellular sub-populations were evaluated by mono-clonal antibodies against various cell surface receptors: CD4/CD8 (T-lymphocytes), CD19 (B-lymphocytes), CD14 (monocytes), and CD56 (natural-killer (NK)-cells). The expressions of dopamine D3 and D4, as well as serotonin 5-HT1A, 5-HT2A, 5-HT2B and 5-HT2C were also assessed. There were no significant differences among the study groups with respect to the frequency of the cellular sub-types, however a unique profound increase in 5-HT2C receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT2C, as well as the NK-cell cyto-toxicity, has been linked with cognitive derangement in dementia. These changes not only corroborate the existence of bi-directional communication between the immune system and the CNS, but also elucidate the role of inflammatory activity in AD pathology, and may serve as potential biomarkers for less invasive and early diagnostic purposes as well.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalJournal of Neuroimmunology
Volume251
Issue number1-2
DOIs
Publication statusPublished - Oct 15 2012

Keywords

  • Aging
  • Alzheimer's disease
  • Dopamine-receptor
  • Leukocyte
  • Natural killer (NK) cell
  • Peripheral blood mono-nuclear cell (PBMC)
  • Serotonin-receptor
  • β-amyloid peptide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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    Martins, L. C. A., Rocha, N. P., Torres, K. C. L., dos Santos, R. R., França, G. S., de Moraes, E. N., Mukhamedyarov, M. A., Zefirov, A. L., Rizvanov, A. A., Kiyasov, A. P., Vieira, L. B., Guimarães, M. M., Yalvaç, M. E., Teixeira, A. L., Bicalho, M. A. C., Janka, Z., Romano-Silva, M. A., Palotás, A., & Reis, H. J. (2012). Disease-specific expression of the serotonin-receptor 5-HT2C in natural killer cells in Alzheimer's dementia. Journal of Neuroimmunology, 251(1-2), 73-79. https://doi.org/10.1016/j.jneuroim.2012.06.003