TY - JOUR
T1 - Disease-specific expression of the serotonin-receptor 5-HT2C in natural killer cells in Alzheimer's dementia
AU - Martins, Luiza Conceição Amorim
AU - Rocha, Natália Pessoa
AU - Torres, Karen Cecília Lima
AU - dos Santos, Rodrigo Ribeiro
AU - França, Giselle Sabrina
AU - de Moraes, Edgar Nunes
AU - Mukhamedyarov, Marat Alexandrovich
AU - Zefirov, Andrey Lvovich
AU - Rizvanov, Albert Anatolyevich
AU - Kiyasov, Andrey Pavlovich
AU - Vieira, Luciene Bruno
AU - Guimarães, Melissa Monteiro
AU - Yalvaç, Mehmet Emir
AU - Teixeira, Antônio Lúcio
AU - Bicalho, Maria Aparecida Camargo
AU - Janka, Zoltán
AU - Romano-Silva, Marco Aurélio
AU - Palotás, András
AU - Reis, Helton José
PY - 2012/10/15
Y1 - 2012/10/15
N2 - 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.
AB - 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.
KW - Aging
KW - Alzheimer's disease
KW - Dopamine-receptor
KW - Leukocyte
KW - Natural killer (NK) cell
KW - Peripheral blood mono-nuclear cell (PBMC)
KW - Serotonin-receptor
KW - β-amyloid peptide
UR - http://www.scopus.com/inward/record.url?scp=84865625787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865625787&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2012.06.003
DO - 10.1016/j.jneuroim.2012.06.003
M3 - Article
C2 - 22766135
AN - SCOPUS:84865625787
SN - 0165-5728
VL - 251
SP - 73
EP - 79
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -