Translocator Protein 18 kDa (TSPO) Deficiency Inhibits Microglial Activation and Impairs Mitochondrial Function

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Abstract

TSPO is mainly expressed in the mitochondrial outer membrane of microglia in the central nervous system, and its expression is greatly increased when microglia are activated. However, the role and mechanism of this protein in microglial activation is not well characterized. In this study, we investigated the role of TSPO in microglial activation by isolating primary microglia from TSPO knockout mice and constructing TSPO-knockdown microglial cell line. We found that TSPO deficiency significantly inhibited microglial activation induced by LPS or IL-4. Mechanistically, TSPO deficiency greatly decreased the mitochondrial membrane potential and ATP production. Moreover, an analysis of cellular energy metabolism showed that TSPO deficiency suppressed mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, resulting in microglial overall metabolic deficits. Together, our results reveal a crucial role of TSPO in microglial activation through the regulation of mitochondrial metabolism, thus providing a potential therapeutic target for neuroinflammation-related diseases of the central nervous system.

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Microglial and macrophage polarization—new prospects for brain repair.

Xiaoming Hu, Rehana Leak, Yejie Shi … (2015)

The traditional view of the adult brain as a static organ has changed in the past three decades, with the emergence of evidence that it remains plastic and has some regenerative capacity after injury. In the injured brain, microglia and macrophages clear cellular debris and orchestrate neuronal restorative processes. However, activation of these cells can also hinder CNS repair and expand tissue damage. Polarization of macrophage populations toward different phenotypes at different stages of injury might account for this dual role. This Perspectives article highlights the specific roles of polarized microglial and macrophage populations in CNS repair after acute injury, and argues that therapeutic approaches targeting cerebral inflammation should shift from broad suppression of microglia and macrophages towards subtle adjustment of the balance between their phenotypes. Breakthroughs in the identification of regulatory molecules that control these phenotypic shifts could ultimately accelerate research towards curing brain disorders.

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Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity.

Dimitris N Xanthos, Jürgen Sandkühler (2013)

The CNS is endowed with an elaborated response repertoire termed 'neuroinflammation', which enables it to cope with pathogens, toxins, traumata and degeneration. On the basis of recent publications, we deduce that orchestrated actions of immune cells, vascular cells and neurons that constitute neuroinflammation are not only provoked by pathological conditions but can also be induced by increased neuronal activity. We suggest that the technical term 'neurogenic neuroinflammation' should be used for inflammatory reactions in the CNS in response to neuronal activity. We believe that neurogenic neuro-inflammation maintains homeostasis to enable the CNS to cope with enhanced metabolic demands and increases the computational power and plasticity of CNS neuronal networks. However, neurogenic neuroinflammation may also become maladaptive and aggravate the outcomes of pain, stress and epilepsy.

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Sodium rutin ameliorates Alzheimer’s disease–like pathology by enhancing microglial amyloid-β clearance

Rui-Yuan Pan, Jun Ma, Xiang-Xi Kong … (2019)

Saltified rutin enhances microglial Aβ clearance, providing a potential therapeutic avenue for Alzheimer’s disease treatment.

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Author and article information

Contributors

Rumeng Yao: URI : https://loop.frontiersin.org/people/922382

Ruiyuan Pan: URI : https://loop.frontiersin.org/people/952825

Jinbo Cheng: URI : https://loop.frontiersin.org/people/858545

Jiangping Xu: URI : https://loop.frontiersin.org/people/952816

Yunfeng Li: URI : https://loop.frontiersin.org/people/311051

Journal

Journal ID (nlm-ta): Front Pharmacol

Journal ID (iso-abbrev): Front Pharmacol

Journal ID (publisher-id): Front. Pharmacol.

Title: Frontiers in Pharmacology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1663-9812

Publication date (Electronic): 30 June 2020

Publication date Collection: 2020

Volume: 11

Electronic Location Identifier: 986

Affiliations

[1] ¹ Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University , Guangzhou, China

[2] ² State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology , Beijing, China

[3] ³ The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences , Beijing, China

[4] ⁴ Institute of Military Veterinary Medicine, Academy of Military Medical Science , Changchun, China

[5] ⁵ The Brain Science Center, Beijing Institute of Basic Medical Sciences , Beijing, China

[6] ⁶ Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine , Nanchang, China

[7] ⁷ Center on Translational Neuroscience, College of Life & Environmental Science, Minzu University of China , Beijing, China

[8] ⁸ Central Laboratory, Southern Medical University , Guangzhou, China

Author notes

Edited by: Hanting Zhang, West Virginia University, United States

Reviewed by: Jun-Xu Li, University at Buffalo, United States; Ying Xu, University at Buffalo, United States

*Correspondence: Jinbo Cheng, cheng_jinbo@ 123456126.com ; Jiangping Xu, jpx@ 123456smu.edu.cn ; Yunfeng Li, lyf619@ 123456aliyun.com

This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology

Article

DOI: 10.3389/fphar.2020.00986

PMC ID: 7339871

PubMed ID: 32695005

SO-VID: 5f747d7f-1f67-4d48-93e8-6d8b673176c1

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 04 March 2020

Date accepted : 18 June 2020

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Figures: 5, Tables: 0, Equations: 0, References: 48, Pages: 10, Words: 4120

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Translocator Protein 18 kDa (TSPO) Deficiency Inhibits Microglial Activation and Impairs Mitochondrial Function

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Most cited references 29

Microglial and macrophage polarization—new prospects for brain repair.

Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity.

Sodium rutin ameliorates Alzheimer’s disease–like pathology by enhancing microglial amyloid-β clearance

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