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Gene expression of serotonergic markers in peripheral blood mononuclear cells of patients with late-onset Alzheimer's disease.

ABSTRACT: Serotonin or 5-hydroxytryptamine (5-HT) is primarily involved in the regulation of learning and memory. Pathological changes in metabolism or functional imbalance of 5-HT has been associated with Alzheimer's disease (AD). The hypothesis tested is that in peripheral blood, markers of the serotonergic pathway can be used as a diagnostic tool for AD. The current study measured the relative expression of 5-HT receptors (5-HTR2A and 5-HTR3A) as well as the 5-HT catalytic enzyme, Monoamine oxidase A (MAO-A) mRNA in Peripheral Blood Mononuclear Cells (PBMCs) of patients with late-onset Alzheimer's disease (LOAD) and age-matched controls. 5-HTR2A, 5-HTR3A, and MAO-A mRNA expressions were examined in PBMCs of 30 patients with LOAD and 30 control individuals. Real-time quantitative PCR was used to measure mRNA expression. The dementia status of patients in this study was assessed using a Mini-Mental State Examination (MMSE). Mean data of relative mRNA expression of 5-HTR2A, 5-HTR3A and MAO-A were significantly lower in PBMCs of patients with LOAD compared with controls. Based on the down-regulation of serotonergic markers in PBMCs, our findings may be another claim to the systemic nature of LOAD. The role of peripheral serotonergic downregulation, in the pathogenesis of AD, needs to be further studied. Given the extremely convenient access to PBMCs, these molecular events may represent more complete dimensions of AD neuropathophysiology or possibly lead to a new direction in studies focused on blood-based markers.

SUBMITTER: Neshan M

PROVIDER: S-EPMC7452509 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Gene expression of serotonergic markers in peripheral blood mononuclear cells of patients with late-onset Alzheimer's disease.

Neshan Masoud M Campbell Arezoo A Malakouti Seyed Kazem SK Zareii Mahsa M Ahangari Ghasem G

Heliyon 20200824 8

Serotonin or 5-hydroxytryptamine (5-HT) is primarily involved in the regulation of learning and memory. Pathological changes in metabolism or functional imbalance of 5-HT has been associated with Alzheimer's disease (AD). The hypothesis tested is that in peripheral blood, markers of the serotonergic pathway can be used as a diagnostic tool for AD. The current study measured the relative expression of 5-HT receptors (5-HTR2A and 5-HTR3A) as well as the 5-HT catalytic enzyme, Monoamine oxidase A ( ...[more]

PMID: 32904297

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Project description:BackgroundPeripheral arterial disease (PAD) is a relatively common manifestation of systemic atherosclerosis that leads to progressive narrowing of the lumen of leg arteries. Circulating monocytes are in contact with the arterial wall and can serve as reporters of vascular pathology in the setting of PAD. We performed gene expression analysis of peripheral blood mononuclear cells (PBMC) in patients with PAD and controls without PAD to identify differentially regulated genes.MethodsPAD was defined as an ankle brachial index (ABI) ≤0.9 (n = 19) while age and gender matched controls had an ABI > 1.0 (n = 18). Microarray analysis was performed using Affymetrix HG-U133 plus 2.0 gene chips and analyzed using GeneSpring GX 11.0. Gene expression data was normalized using Robust Multichip Analysis (RMA) normalization method, differential expression was defined as a fold change ≥1.5, followed by unpaired Mann-Whitney test (P < 0.05) and correction for multiple testing by Benjamini and Hochberg False Discovery Rate. Meta-analysis of differentially expressed genes was performed using an integrated bioinformatics pipeline with tools for enrichment analysis using Gene Ontology (GO) terms, pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular event enrichment using Reactome annotations and network analysis using Ingenuity Pathway Analysis suite. Extensive biocuration was also performed to understand the functional context of genes.ResultsWe identified 87 genes differentially expressed in the setting of PAD; 40 genes were upregulated and 47 genes were downregulated. We employed an integrated bioinformatics pipeline coupled with literature curation to characterize the functional coherence of differentially regulated genes.ConclusionNotably, upregulated genes mediate immune response, inflammation, apoptosis, stress response, phosphorylation, hemostasis, platelet activation and platelet aggregation. Downregulated genes included several genes from the zinc finger family that are involved in transcriptional regulation. These results provide insights into molecular mechanisms relevant to the pathophysiology of PAD.

Dataset Information

Gene expression of serotonergic markers in peripheral blood mononuclear cells of patients with late-onset Alzheimer's disease.

Publications

Gene expression of serotonergic markers in peripheral blood mononuclear cells of patients with late-onset Alzheimer's disease.

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