Activation of NMDAR/Ca2+/CaKMII/ROS pathway by Brucella induced neuronal cell apoptosis

IF 2.9 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology Pub Date : 2025-04-17 DOI:10.1016/j.jneuroim.2025.578620

Meiling Liu , Hongfang Yu , Yuzhe Wang , Shujun Shi , Haixin Liu , Xiuyun Cao , Liping Sun , Hao Yang , Zhelin Zhang

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引用次数: 0

Abstract

Background

Neurobrucellosis is an inflammatory disease of the central nervous system caused by brucellosis and is the most serious form of brucellosis. However, the pathogenesis of this disease is not well understood, and there are no suitable molecular markers for rapid diagnosis. In the present study, we infected neuronal cells and brain slices with cerebrospinal fluid from patients with bruceopathy.

Methods

Neuron-specific enolase (NSE) levels were detected by immunofluorescence. Nissl staining, HE staining and transmission electron microscopy were used to observe nissl bodies and physiological. Calcium ion flow was detected by calcium ion fluorescence probe. The expression levels of related molecules were detected. Reactive oxygen species (ROS) levels and mitochondrial membrane potential were also measured.

Results

The cerebrospinal fluid infected neurons and brain slice and activated kynurenine pathway (KP) lead to excessive activation of N-methyl-d-aspartate receptor (NMDAR), increased calcium flow, depolarization of mitochondrial membrane potential and increased ROS levels. This eventually leads to increased central nervous system (CNS) damage. The KP product quinolinic acid (QUIN) showed the same results as after infection with Brucella S2308.

Conclusion

Collectively, our study supports that Brucella neurotype causes CNS damage via QUIN/NMDAR/Ca²⁺/CaKMII/ROS, which provides one possible therapeutic target for neurobrucellosis.

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布鲁氏菌激活NMDAR/Ca2+/CaKMII/ROS通路诱导神经元细胞凋亡

背景：神经布鲁氏菌病是由布鲁氏菌病引起的中枢神经系统炎症性疾病，是最严重的布鲁氏菌病。然而，该病的发病机制尚不清楚，也没有合适的分子标记物用于快速诊断。在本研究中，我们用脑脊液感染脑路病变患者的神经元细胞和脑切片。方法采用免疫荧光法检测神经元特异性烯醇化酶（NSE）水平。采用尼氏染色、HE染色及透射电镜观察尼氏体及生理变化。用钙离子荧光探针检测钙离子流动。检测相关分子的表达水平。同时测定活性氧（ROS）水平和线粒体膜电位。结果脑脊液感染神经元和脑切片，激活犬尿氨酸通路（KP），导致n -甲基-d-天冬氨酸受体（NMDAR）过度激活，钙流量增加，线粒体膜电位去极化，ROS水平升高。这最终会导致中枢神经系统（CNS）损伤加重。KP产物喹啉酸（QUIN）与感染布鲁氏菌S2308后的结果相同。综上所述，本研究支持神经型布鲁氏菌通过QUIN/NMDAR/Ca2+/CaKMII/ROS引起中枢神经系统损伤，为神经型布鲁氏菌病提供了一种可能的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of neuroimmunology 医学-免疫学

CiteScore

6.10

自引率

3.00%

发文量

154

审稿时长

37 days

期刊介绍： The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.