title: Disease-specific expression of the serotonin-receptor 5-HT(2C) in natural killer cells in Alzheimer's dementia.
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 D(3) and D(4), as well as serotonin 5-HT(1A), 5-HT(2A), 5-HT(2B) and 5-HT(2C) 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-HT(2C) receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT(2C), 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.
authors: Laboratório de Neurociência, Instituto Nacional de Ciência e Tecnologia (INCT) de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena 190, 30130-100 Belo Horizonte, Minas Gerais, Brazil.
authors: Luiza Conceição Amorim
authors: LC
authors: Martins
authors: Natália Pessoa
authors: NP
authors: Rocha
authors: Karen Cecília Lima
authors: KC
authors: Torres
authors: Rodrigo Ribeiro
authors: RR
authors: Dos Santos
authors: Giselle Sabrina
authors: GS
authors: França
authors: Edgar Nunes
authors: EN
authors: de Moraes
authors: Marat Alexandrovich
authors: MA
authors: Mukhamedyarov
authors: Andrey Lvovich
authors: AL
authors: Zefirov
authors: Albert Anatolyevich
authors: AA
authors: Rizvanov
authors: Andrey Pavlovich
authors: AP
authors: Kiyasov
authors: Luciene Bruno
authors: LB
authors: Vieira
authors: Melissa Monteiro
authors: MM
authors: Guimarães
authors: Mehmet Emir
authors: ME
authors: Yalvaç
authors: Antônio Lúcio
authors: AL
authors: Teixeira
authors: Maria Aparecida Camargo
authors: MA
authors: Bicalho
authors: Zoltán
authors: Z
authors: Janka
authors: Marco Aurélio
authors: MA
authors: Romano-Silva
authors: András
authors: A
authors: Palotás
authors: Helton José
authors: HJ
authors: Reis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003863:Depression / Q000378:metabolism; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D044405:Receptor, Serotonin, 5-HT2C / Q000096:biosynthesis*; D050637:Receptors, Dopamine D3 / Q000096:biosynthesis; D050638:Receptors, Dopamine D4 / Q000096:biosynthesis; D011985:Receptors, Serotonin / Q000096:biosynthesis
chemical_list: D044405:Receptor, Serotonin, 5-HT2C; D050637:Receptors, Dopamine D3; D011985:Receptors, Serotonin; D050638:Receptors, Dopamine D4