RESUMO
BACKGROUND: Abnormal activation of immune system is an important pathogenesis of Parkinson's disease, but the relationship between peripheral inflammation, central microglia activation and dopaminergic degeneration remains unclear. OBJECTIVES: To evaluate the brain regional microglia activation and its relationship with clinical severity, dopaminergic presynaptic function, and peripheral inflammatory biomarkers related to adaptive immunity. METHODS: In this case-control study, we recruited 23 healthy participants and 24 participants with early-stage Parkinson's disease. 18F-PBR06 PET/MR for microglia activation, 18F-FP-DTBZ for dopaminergic denervation, total account of T cells and subpopulations of T helper (Th1/Th2/Th17) cells, and the levels of serum inflammatory cytokines were assessed. Sanger sequencing was used to exclude the mix-affinity binders of 18F-PBR06-PET. RESULTS: Compared to healthy controls, patients with Parkinson's disease had an increased 18F-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. 18F-PBR06-PET SUVR was positively associated with 18F-FP-DTBZ-PET SUVR in the brainstem and not associated with disease severity measured by Hoehn and Yahr stage, MDS-UPDRS III scores. Patients with Parkinson's disease had elevated frequencies of Th1 cells and serum levels of IL10 and IL17A as compared to healthy controls. No significant association between peripheral inflammation markers and microglia activation in the brain of PD was observed. CONCLUSION: Parkinson's disease is associated with early putaminal microglial activation and peripheral phenotypic Th1 bias. Peripheral adaptive immunity might be involved in microglia activation in the process of neurodegeneration in PD indirectly, which may be a potential biomarker for the early detection and the target for immunomodulating therapy.
Assuntos
Doença de Parkinson , Imunidade Adaptativa , Encéfalo/patologia , Estudos de Casos e Controles , Dopamina , Humanos , Inflamação , Microglia/patologia , Doença de Parkinson/patologia , Tomografia por Emissão de PósitronsRESUMO
Whether aging or Parkinson's disease (PD) affects the responses of peripheral blood mononuclear cells (PBMCs) to immunosuppression by bone marrowderived mesenchymal stem cell (BMMSCs) and which cytokines are more effective in inducing BMMSCs to be immunosuppressive remains to be elucidated. PBMCs were isolated from healthy young (age 2635), healthy middleaged (age 5660) and middleaged PDaffected individuals. All the recruits were male. The mitogenstimulated PBMCs and proinflammatory cytokinepretreated BMMSCs were cocultured. The PBMC proliferation was measured using Cell Counting Kit8, while the cytokine secretion was assayed by cytometric bead array technology. The immunosuppressive ability of BMMSCs was confirmed in young healthy, middleaged healthy and middleaged PDaffected individuals. Among the three groups, the PBMC proliferation and cytokine secretion of the young healthy group were suppressed more significantly compared with those of the middleaged healthy and middleaged PDaffected group. No significant differences were identified in the PBMC proliferation and cytokine secretion between the patients with PD and the middleaged healthy subjects. Interferon (IFN)γ synergized with tumor necrosis factor (TNF)α, interleukin (IL)1α or IL1ß was more effective than either one alone, and the combinations of IFNγ + IL1α and IFNγ + IL1ß were more effective than IFNγ + TNFα in inducing BMMSCs to inhibit PBMC proliferation. The results of the present study suggested that aging, rather than PD, affects the response of PBMCs toward the suppression of BMMSC, at least in middleaged males. Patients with PD aged 5660 remain eligible for antiinflammatory BMMSCbased therapy. Treatment of BMMSCs with IFNγ + IL1α or IFNγ + IL1ß prior to transplantation may result in improved immunosuppressive effects.