Objective: To investigate the effect of silencing P2X7 receptor (P2X7R) by RNA interference on microglial phagocytosis of amyloid-β (Aβ) protein and to explore its possible mechanism.
Methods: The small interfering RNA (siRNA) targeting the P2X7R gene was identified. The microglial cells activated by Aβ1-42 were infected with the Lipofectamine-siP2X7R and it was designated as siP2X7R group. Microglia infected with Lipofectamine-siNC was designated as siNC group and non-infected cells as con group. The levels of P2X7R mRNA were detected by real-time PCR and the P2X7R protein was determined by Western blotting. The levels of IL-1β and TNF-α were measured by ELISA. The microglial phagocytosis of Aβ1-42 was observed by ELISA and immunocytochemistry staining.
Results: Detected by the Real-time PCR, the expression level of P2X7R mRNA of siP2X7R group decreased significantly versus siNC and con groups (P<0.05). The lowered expression of P2X7R protein detected by Western blotting was consistent with Real-time PCR. After RNA interference silencing P2X7R, the levels of IL-1β and TNF-α detected by ELISA in siP2X7R group less than those in con, siNC groups, significantly (P<0.05). In con, siNC and siP2X7R groups respectively, the levels of Aβ1-42 in supernatant were (423±20) pg/ml, (417±16) pg/ml, (296±30) pg/ml and the levels of Aβ1-42 in the microglia were (190±37) pg/ml, (187±39) pg/ml, (322±26) pg/ml. Compared to siNC and con groups, in siP2X7R group the levels of Aβ1-42 in supernatant decreased (P<0.05) and the levels of Aβ1-42 in the microglia increased (P<0.05). Aβ1-42 immunofluorescence staining showed that the red fluorescent products were seen in the cytoplasm of most microglias in siP2X7R group, but in con or siNC groups in only few microglias these products were depicted.
Conclusions: The silence expression of P2X7R by RNA interference effectively decreases the levels of IL-1β and TNF-α released by microglia and promotes microglia to phagocytose Aβ. P2X7R could be used as an effective therapeutic target for RNA interference treatment of Alzheimer's disease.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Schisandra chinensis lignans exerts endocannabinoids-like antidepressive effect: the phagocytotic relationship of activated CB2R-mediated M2 microglia and "stressed-but-viable" neuron.
J Ethnopharmacol
January 2025
Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China. Electronic address:
Ethnopharmacological Relevance: Schisandra chinensis, a traditional functional Chinese medicine, is known for its ability to tonify the kidneys, calm the heart, and tranquilize the mind. Recent pharmacological research has demonstrated its anti-inflammatory and neuroprotective effects.
Aim Of The Study: We had previously demonstrated that Schisandra chinensis lignans (SCL) promote microglia polarization to M2 phenotype via targeting cannabinoid receptor type-2 (CB2R) to exert antidepressant effects.
CHIT1 regulates the neuroinflammation and phagocytosis of microglia and suppresses Aβ plaque deposition in Alzheimer's disease.
J Pathol
January 2025
Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
Chitinase 1 (CHIT1), as a chitin-specific hydrolase, significantly influences the progression of Alzheimer's disease (AD) through microglia-associated inflammation and amyloid beta (Aβ) plaque accumulation. However, the precise mechanism of CHIT1 action in AD remains uncertain. The effects of CHIT1 on cerebral blood flow (CBF), hippocampal volume, and cognitive function were investigated in APP/PS1 mice.
View Article and Find Full Text PDFCD11c-Expressing Microglia Are Transient, Driven by Interactions With Apoptotic Cells.
Glia
January 2025
Department of Neurobiology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Microglia, the parenchymal macrophage of the central nervous system, serve crucial remodeling functions throughout development. Microglia are transcriptionally heterogenous, suggesting that distinct microglial states confer discrete roles. Currently, little is known about how dynamic these states are, the cues that promote them, or how they impact microglial function.
View Article and Find Full Text PDFPuerarin mitigates cognitive decline and white matter injury via CD36-Mediated microglial phagocytosis in chronic cerebral hypoperfusion.
Phytomedicine
January 2025
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, China; Jiangxi Provincial Key Laboratory of Nervous System Tumors and Cerebrovascular Diseases, Nanchang University, Nanchang, Jiangxi, China; JXHC Key Laboratory of Neurological Medicine, Nanchang University, Nanchang, Jiangxi, China; Jiangxi Provincial Key Laboratory of Neurological Diseases, Nanchang University, Nanchang, Jiangxi, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi 330000, China. Electronic address:
Background: Chronic cerebral hypoperfusion (CCH) contributes significantly to white matter injury (WMI) and cognitive impairment, often leading to vascular dementia (VaD). Inefficient clearance of myelin debris by microglia impedes white matter repair, making microglia-mediated myelin clearance a promising therapeutic strategy for WMI. Puerarin (Pu), an isoflavonoid monomer from Pueraria lobata, is known for its neuroprotective, anti-inflammatory, and immunoregulatory properties.
View Article and Find Full Text PDFTreadmill Exercise Mitigates Alzheimer's Pathology by Modulating Glial Polarization and Reducing Oligodendrocyte Precursor Cell Perivascular Clustering.
Med Sci Sports Exerc
January 2025
School of Physical Education and Sports Science, South China Normal University, Guangzhou, CHINA.
Purpose: This study aimed to investigate the pathological responses of glial cells at different distances from amyloid plaques and the characteristics of oligodendrocyte precursor cells (OPCs) in perivascular clustering. Additionally, it sought to explore the impact of exercise training on AD pathology, specifically focusing on the modulation of glial responses and the effects of OPC perivascular clustering.
Methods: Three-month-old C57BL/6 and APP/PS1 mice were divided into four groups: wild-type sedentary, wild-type exercise, sedentary AD, and exercise AD groups.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!