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

Autor: Martins, L.C.A., Rocha, N.P., Torres, K.C.L., dos Santos, R.R., França, G.S., de Moraes, E.N., Reis, H.J.
Přispěvatelé: Martins, L.C.A., Rocha, N.P., Torres, K.C.L., dos Santos, R.R., França, G.S., de Moraes, E.N., Reis, H.J., Yeditepe Üniversitesi
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Popis: 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 ß-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. © 2012 Elsevier B.V. Conselho Nacional de Desenvolvimento Científico e Tecnológico Conselho Nacional de Desenvolvimento Científico e Tecnológico Fundação de Amparo à Pesquisa do Estado de Minas Gerais Coordenação de Aperfeiçoamento de Pessoal de Nível Superior This work was supported by the Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico ( CNPq ) , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) , and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) , as well as by Asklepios-Med (Hungary) .
Databáze: OpenAIRE