九州大学 · Neuroscience
타카히로 마스다 교수의 연구실은 중추신경계에서의 미세아교세포의 이질성과 활성화 메커니즘을 중심으로, 신경 손상 및 신경병성 통증과 관련된 미세아교세포의 전사적 조절 체계를 규명하고 있습니다. 특히 IRF8, IRF5, IL-1β 등 핵심 전사인자가 미세아교세포의 반응성 표현형 전환에 어떻게 기여하는지, 그리고 ATP 유출 메커니즘을 통해 통증 반응이 유도되는지를 단계적으로 밝혀내고 있습니다. 고해상도 단세포 분석 기술과 유전자 조작 모델을 융합한 연구로, 뇌질환의 새로운 치료 타겟을 탐색하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Microglia are resident immune cells in the central nervous system (CNS) that are capable of carrying out prominent and various functions during development and adulthood under both homeostatic and disease conditions. Although microglia are traditionally thought to be heterogeneous populations, which potentially allows them to achieve a wide range of responses to environmental changes for the maintenance of CNS homeostasis, a lack of unbiased and high-throughput methods to assess microglia hetero
Microglia become activated by multiple types of damage in the nervous system and play essential roles in neuronal pathologies. However, how microglia transform into reactive phenotypes is poorly understood. Here, we identify the transcription factor interferon regulatory factor 8 (IRF8) as a critical regulator of reactive microglia. Within the spinal cord, IRF8 expression was normally low; however, the expression was markedly upregulated in microglia, but not in neurons or astrocytes, after peri
In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the purinergic P2X4 receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de n
Activation of purinergic receptors in the spinal cord by extracellular ATP is essential for neuropathic hypersensitivity after peripheral nerve injury (PNI). However, the cell type responsible for releasing ATP within the spinal cord after PNI is unknown. Here we show that PNI increases expression of vesicular nucleotide transporter (VNUT) in the spinal cord. Extracellular ATP content ([ATP]e) within the spinal cord was increased after PNI, and this increase was suppressed by exocytotic inhibito
Interferon regulatory factor-8 (IRF8) plays a crucial role in the transformation of microglia to a reactive state by regulating the expression of various genes. In the present study, we show that IRF1 is required for IRF8-induced gene expression in microglia. Peripheral nerve injury induced IRF1 gene upregulation in the spinal microglia in an IRF8-dependent manner. IRF8 transduction in cultured microglia induced de novo gene expression of IRF1. Importantly, knockdown of the IRF1 gene in IRF8-tra
Microglia are the resident monocytic cells in the central nervous system (CNS), where they constitute the complex tissue structure together with a diverse set of cell-types, including neurons, glial cells, and vasculature. Different from other cells, microglia have distinct features, including not only their origin but functions in the CNS, and serve multiple roles within healthy and diseased CNS tissue. The present review highlights the latest advance in our understanding of the nature of micro
The central nervous system (CNS) hosts a variety of immune cells, including two distinct macrophage populations: microglia are found in the parenchyma, whereas CNS-associated macrophages (CAMs) cover the CNS interfaces, such as the perivascular spaces, the meninges and the choroid plexus. Recent studies have given novel insights into the nature of CAMs as compared to microglia. In this mini-review, we summarise the current knowledge about the ontogenetic relationship and the underlying mechanism
