Subthalamic nucleus deep brain stimulation suppresses neuroinflammation by Fractalkine pathway in Parkinson’s disease rat model

Chen, Yingchuan; Zhu, Guanyu; Liu, Defeng; Zhang, Xin; Liu, Yuye; Yuan, Tianshuo; Du, Tingting; Zhang, Jianguo

doi:10.1016/j.bbi.2020.07.035

Cited by 34 publications

(24 citation statements)

References 33 publications

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“…In patients with poor neurological outcomes, decreased levels of plasma CX 3 CL1 persisted up to 180 days after stroke injury compared with patients with better outcomes. In keeping with these findings, brain tissue from human patients and rats with subarachnoid hemorrhage had lower expression of CX 3 CL1 and CX 3 CR1 as well as enhanced microglial activation and neuroinflammation (119).…”

Section: Role Of CX 3 Cl1-cx 3 Cr1 In Vascular Inflammationsupporting

confidence: 72%

Role of the CX₃CL1-CX₃CR1 axis in renal disease

Hamdan

Robinson

2021

American Journal of Physiology-Renal Physiology

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Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

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Section: Role Of CX 3 Cl1-cx 3 Cr1 In Vascular Inflammationsupporting

confidence: 72%

Role of the CX₃CL1-CX₃CR1 axis in renal disease

Hamdan

Robinson

2021

American Journal of Physiology-Renal Physiology

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“…Moreover, Chen et al showed that electrical stimulation of anterior thalamic nuclei in the field of epilepsy downregulated inflammatory processes in the hippocampus, leading to a reduction of neuronal loss and neurogenesis in a rat model (Chen et al, 2017). Similar results were obtained in a Parkinson disease (PD) rat model, in which subthalamic nucleus-DBS-suppressed neuroinflammation and led to an increased survival of dopaminergic neurons in the substantia nigra (Chen et al, 2020). In addition, Dandekar et al showed a significant downregulation of the inflammatory mediators IL-5 and IL-18 in the hippocampus and of IL-6 in the nucleus accumbens after seven days of DBS of the medial forebrain bundle in a depression model (Dandekar et al, 2019).…”

Section: Introductionmentioning

confidence: 73%

Influence of Simulated Deep Brain Stimulation on the Expression of Inflammatory Mediators by Human Central Nervous System Cells In Vitro

et al. 2021

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Deep brain stimulation (DBS) seems to modulate inflammatory processes. Whether this modulation leads to an induction or suppression of inflammatory mediators is still controversially discussed. Most studies of the influence of electrical stimulation on inflammation were conducted in rodent models with direct current stimulation and/or long impulses, both of which differ from the pattern in DBS. This makes comparisons with the clinical condition difficult. We established an in-vitro model that simulated clinical stimulation patterns to investigate the influence of electrical stimulation on proliferation and survival of human astroglial cells, microglia, and differentiated neurons. We also examined its influence on the expression of the inflammatory mediators C-X-C motif chemokine (CXCL)12, CXCL16, CC-chemokin-ligand-2 (CCL)2, CCL20, and interleukin (IL)-1β and IL-6 by these cells using quantitative polymerase chain reaction. In addition, protein expression was assessed by immunofluorescence double staining. In our model, electrical stimulation did not affect proliferation or survival of the examined cell lines. There was a significant upregulation of CXCL12 in the astrocyte cell line SVGA, and of IL-1β in differentiated SH-SY5Y neuronal cells at both messenger RNA and protein levels. Our model allowed a valid examination of chemokines and cytokines associated with inflammation in human brain cells. With it, we detected the induction of inflammatory mediators by electrical stimulation in astrocytes and neurons.

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“…Interestingly, invasive electrical stimulation of other brain regions also attenuates neuroinflammation: high-frequency deep brain stimulation (DBS) (130 Hz) of the anterior thalamic nucleus resulted in a decrease of TNF-α and IL-1β in a rat model of epilepsy [21]. Similarly, DBS of the subthalamic nucleus revealed a reduced level of IL-1β in the substantia nigra of a rat model of Parkinson's disease [20].…”

Section: Discussionmentioning

confidence: 99%

“…In stimulated rats, ChAT + CD4 + -cells were significantly more abundant in the lesioned brain hemisphere compared to sham animals (ChAT + CD4 + -cells stim vs. sham: 0.15 [IQR 0.13-0.21] vs. 0.07 [IQR 0.02-0.07], ChAT + CD4 + -cells/cells of ROI, * p < 0.05, n = 4/group; Figure 2B,C). The receptor polypeptide α7nAchR, responding to the neurotransmitter acetylcholine, is expressed in many regions of the central and peripheral nervous system but also on non-neuronal cells including astrocytes and microglia [20][21][22]. Activation of α7nAchR via receptor agonists results in anti-inflammatory effects such as a decrease in the synthesis of cytokines and chemokines [23,24].…”

Section: Mlr-hfs Is Associated With An Increased Number Of Chat Expressing Cells But Does Not Change the Amount Of α7nachr-positive Cellsmentioning

confidence: 99%

Mesencephalic Electrical Stimulation Reduces Neuroinflammation after Photothrombotic Stroke in Rats by Targeting the Cholinergic Anti-Inflammatory Pathway

Schuhmann

Papp

Stoll

et al. 2021

IJMS

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Inflammation is crucial in the pathophysiology of stroke and thus a promising therapeutic target. High-frequency stimulation (HFS) of the mesencephalic locomotor region (MLR) reduces perilesional inflammation after photothrombotic stroke (PTS). However, the underlying mechanism is not completely understood. Since distinct neural and immune cells respond to electrical stimulation by releasing acetylcholine, we hypothesize that HFS might trigger the cholinergic anti-inflammatory pathway via activation of the α7 nicotinic acetylcholine receptor (α7nAchR). To test this hypothesis, rats underwent PTS and implantation of a microelectrode into the MLR. Three hours after intervention, either HFS or sham-stimulation of the MLR was applied for 24 h. IFN-γ, TNF-α, and IL-1α were quantified by cytometric bead array. Choline acetyltransferase (ChAT)+ CD4+-cells and α7nAchR+-cells were quantified visually using immunohistochemistry. Phosphorylation of NFĸB, ERK1/2, Akt, and Stat3 was determined by Western blot analyses. IFN-γ, TNF-α, and IL-1α were decreased in the perilesional area of stimulated rats compared to controls. The number of ChAT+ CD4+-cells increased after MLR-HFS, whereas the amount of α7nAchR+-cells was similar in both groups. Phospho-ERK1/2 was reduced significantly in stimulated rats. The present study suggests that MLR-HFS may trigger anti-inflammatory processes within the perilesional area by modulating the cholinergic system, probably via activation of the α7nAchR.

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Subthalamic nucleus deep brain stimulation suppresses neuroinflammation by Fractalkine pathway in Parkinson’s disease rat model

Cited by 34 publications

References 33 publications

Role of the CX₃CL1-CX₃CR1 axis in renal disease

Role of the CX₃CL1-CX₃CR1 axis in renal disease

Influence of Simulated Deep Brain Stimulation on the Expression of Inflammatory Mediators by Human Central Nervous System Cells In Vitro

Mesencephalic Electrical Stimulation Reduces Neuroinflammation after Photothrombotic Stroke in Rats by Targeting the Cholinergic Anti-Inflammatory Pathway

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Subthalamic nucleus deep brain stimulation suppresses neuroinflammation by Fractalkine pathway in Parkinson’s disease rat model

Cited by 34 publications

References 33 publications

Role of the CX3CL1-CX3CR1 axis in renal disease

Role of the CX3CL1-CX3CR1 axis in renal disease

Influence of Simulated Deep Brain Stimulation on the Expression of Inflammatory Mediators by Human Central Nervous System Cells In Vitro

Mesencephalic Electrical Stimulation Reduces Neuroinflammation after Photothrombotic Stroke in Rats by Targeting the Cholinergic Anti-Inflammatory Pathway

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Role of the CX₃CL1-CX₃CR1 axis in renal disease

Role of the CX₃CL1-CX₃CR1 axis in renal disease