Microglial translocator protein and stressor-related disorder. (November 2020)

• Record Type: Journal Article
• Authors: Kikutani, Kazuya; Giga, Hiroshi; Hosokawa, Koji; Shime, Nobuaki; Aizawa, Hidenori
• Is Part Of: Neurochemistry international. Volume 140(2020)
• Publication Date: 2020-11
• Subjects: Microglia -- Translocator protein -- Depression -- Anxiety -- Post-intensive care syndrome; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2020.104855
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Despite the prevalence of neuroinflammation in psychiatric disorders, molecular mechanism underlying it remains elusive. Translocator protein 18 kDa (TSPO), also known as peripheral benzodiazepine receptor, is a mitochondrial protein implicated in the synthesis of steroids in a variety of tissues. Multiple reports have shown increased expression of TSPO in the activated microglia in the CNS. Radioactive probes targeting TSPO have been developed and used for imaging assessment in neurological and psychiatric disorders to examine neuroinflammation. Recent studies revealed that the wide range of stressors ranging from psychological to physical insults induced TSPO in human, suggesting that this protein could be an important tool to explore the contribution of microglia in stressor-related disorders. In this review, we first overview the microglial activation with TSPO in a wide range of stressors in human and animal models to discuss prevalent roles of TSPO in response of CNS to stressors. With recent update of the signaling pathway revealing link connecting TSPO with neuroinflammatory effectors such as reactive oxygen species, we discuss TSPO as a therapeutic targeting tool for suppression of adverse effect of stressors on long-lasting changes in animal behaviors and activities. Targeting TSPO which mediates neuroinflammation under the stress might pave the way to develop therapeutic intervention and prophylaxis of stressor-related disorder. Highlights: Exposure to a wide range of stressors induces TSPO in the activated microglia. Upregulation of TSPO exerts inflammatory functions via multifaceted pathways. TSPO may be a target for drug development for stressor-related disorder.