The Role of XIST in Parkinson’s Disease: As a ceRNA to Adsorb miR-155-5p to Upregulate BDNF Expression and Relive Neuroinflammation

Abstract

Background: Parkinson’s disease (PD) belongs to the chronic progressive disease of the nervous system and dopaminergic neuron defects is its major characteristic. Before research have indicated that the growth and survival of neurons were affected by the brain-derived neurotrophic factor (BDNF). Nonetheless, the function of BDNF and its regulatory mechanisms in the neuroinflammation of PD is not clear, further investigation is needed. Methods: Immunohistochemistry (IHC) assay were used to determine the levels of α-synuclein and tyrosine hydroxylase (TH)-positive neurons. Further, pole tests and accelerating rotarod tests were conducted to carry out the time-on-pole and time-on-rod behavioral measurements. Immunofluorescence staining assay was used to detect the expression of BDNF. Besides, RT-qPCR assays were used to measure the mRNA expression of XIST and miR-155-5p. And the luciferase reporter assays were used to examine the binding ability of XIST (or BDNF) and microRNA (miR)-155-5p. In addition, enzyme linked immunosorbent assays (ELISA) were implemented to verify the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. Results: First, the PD mouse model were established successfully through MPTP injections. Results found that the BDNF showed low expression levels in the PD mice, but upregulated BDNF expression was relevant to the relieved PD progression. In regulatory mechanisms respect, it was exhibited that the XIST regulate BDNF by adsorbing miR-155-5p. The rescue assays were also conducted, results showed that the XIST/miR-155-5p/BDNF competing with endogenous (ce)RNA axis to influence PD progression, and XIST modulated miR-155-5p to regulate neuroinflammation through the BDNF/tropomyosin receptor kinase B (TrkB)/myeloid differentiation primary response 88 (MyD88) pathway. Moreover, ANA-12, a TrkB antagonist, was shown to reverse the influence of BDNF on PD progression. Conclusions: It is revealed that XIST adsorb miR-155-5p to regulate BDNF expression and reduce neuroinflammation in PD via acting as a ceRNA.