C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-01-13 DOI:10.1111/cns.70216

Xiaoling Peng, Jie Ju, Zheng Li, Jie Liu, Xiaoqian Jia, Jihong Wang, Jihao Ren, Feng Gao

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引用次数: 0

Abstract

Aims

Communication within glial cells acts as a pivotal intermediary factor in modulating neuroimmune pathology. Meanwhile, an increasing awareness has emerged regarding the detrimental role of glial cells and neuroinflammation in morphine tolerance (MT). This study investigated the influence of crosstalk between astrocyte and microglia on the evolution of morphine tolerance.

Methods

Sprague-Dawley rats were intrathecally treated with morphine twice daily for 9 days to establish morphine-tolerant rat model. Tail-flick latency test was performed to identify the analgesic effect of morphine. The role of microglia, astrocyte and C3-C3aR axis in morphine tolerance were elucidated by real-time quantitative polymerase chain reaction, Western blot, and immunofluorescence.

Results

Chronic morphine treatment notably promoted the activation of microglia, upregulated the production of proinflammatory mediators (interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα), and complement component 1q (C1q)). Simultaneously, it programed astrocytes to a pro-inflammatory phenotype (A1), which mainly expresses complement 3 (C3) and serping1. PLX3397 (a colony-stimulating factor 1 receptor (CSF1R) inhibitor), Compstain (a C3 inhibitor) and SB290157(a C3aR antagonist) could reverse the above pathological process and alleviate morphine tolerance to different extents.

Conclusion

Our findings identify C3-C3aR axis as an amplifier of microglia-astrocyte crosstalk, neuroinflammation and a node for therapeutic intervention in morphine tolerance.

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.