Microglial translocator protein and stressor-related disorder
Kazuya Kikutani1, Hiroshi Giga1, Koji Hosokawa1
1Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Science, Hiroshima University, Japan.
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.
Insights
Translocator protein 18 kDa (TSPO) is upregulated in neuroinflammation and activated microglia. Targeting TSPO offers a potential therapeutic strategy for stressor-related psychiatric disorders.
Area of Science:
- Neuroscience
- Psychiatry
- Molecular Biology
Background:
- Neuroinflammation is prevalent in psychiatric disorders, but its molecular mechanisms are not fully understood.
- Translocator protein 18 kDa (TSPO), a mitochondrial protein, is increasingly expressed in activated microglia within the central nervous system (CNS).
- TSPO is involved in steroid synthesis and its expression is induced by various stressors in humans.
Purpose of the Study:
- To review microglial activation and TSPO expression in response to stressors in human and animal models.
- To discuss the role of TSPO in the CNS's response to stressors.
- To explore TSPO as a therapeutic target for stressor-related disorders.
Main Methods:
- Literature review of studies on microglial activation and TSPO.
- Analysis of signaling pathways linking TSPO to neuroinflammatory effectors like reactive oxygen species.
- Examination of TSPO's role in stressor-induced behavioral changes.
Main Results:
- TSPO expression is increased in activated microglia in the CNS under various stress conditions.
- TSPO signaling is linked to neuroinflammatory pathways, including reactive oxygen species.
- Targeting TSPO may suppress adverse effects of stressors on behavior.
Conclusions:
- TSPO is a key player in the CNS response to stressors and neuroinflammation.
- Targeting TSPO presents a promising therapeutic avenue for stressor-related psychiatric disorders.
- Further research into TSPO-mediated neuroinflammation could lead to novel interventions.
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