Robert Stempel College of Public Health & Social Work, Environmental Health Sciences, Cognitive Neuroscience & Imaging Florida International University, 11200 SW 8(th) St, AHC5-507, Miami, FL 33199, USA.
Pharmacol Ther. 2019 Feb;194:44-58. doi: 10.1016/j.pharmthera.2018.09.003. Epub 2018 Sep 4.
The use of Translocator Protein 18 kDa (TSPO) as a clinical neuroimaging biomarker of brain injury and neuroinflammation has increased exponentially in the last decade. There has been a furious pace in the development of new radiotracers for TSPO positron emission tomography (PET) imaging and its use has now been extensively described in many neurological and mental disorders. This fast pace of research and the ever-increasing number of new laboratories entering the field often times lack an appreciation of the historical perspective of the field and introduce dogmatic, but unproven facts, related to the underlying neurobiology of the TSPO response to brain injury and neuroinflammation. Paradoxically, while in neurodegenerative disorders and in all types of CNS pathologies brain TSPO levels increase, a new observation in psychiatric disorders such as schizophrenia is decreased brain levels of TSPO measured by PET. The neurobiological bases for this new finding is currently not known, but rigorous experimental design using multiple experimental approaches and careful interpretation of results is critically important to provide the methodological and/or biological underpinnings to this new observation. This review provides a perspective of the early history of validating TSPO as a biomarker of brain injury and neuroinflammation and a critical analysis of controversial topics in the literature related to the cellular sources of the TSPO response. The latter is important in order to provide the correct interpretation of PET studies in neurodegenerative and psychiatric disorders. Furthermore, this review proposes some yet to be explored explanations to new findings in psychiatric disorders and new approaches to quantitatively assess the glial sources of the TSPO response in order to move the field forward.
在过去十年中，使用 18 kDa 转位蛋白（TSPO）作为脑损伤和神经炎症的临床神经影像学生物标志物的应用呈指数级增长。新型 TSPO 正电子发射断层扫描（PET）放射性示踪剂的开发步伐迅猛，其在许多神经和精神疾病中的应用已得到广泛描述。这种研究的快速发展以及越来越多的新实验室进入该领域，往往缺乏对该领域历史背景的了解，并引入了一些与 TSPO 对脑损伤和神经炎症的反应的潜在神经生物学相关的教条但未经证实的事实。矛盾的是，虽然在神经退行性疾病和所有类型的中枢神经系统疾病中，大脑 TSPO 水平增加，但在精神疾病（如精神分裂症）中观察到一个新现象，即通过 PET 测量大脑 TSPO 水平降低。目前尚不清楚这种新发现的神经生物学基础，但使用多种实验方法进行严格的实验设计和对结果的仔细解释对于为这一新观察结果提供方法学和/或生物学基础至关重要。本文回顾了 TSPO 作为脑损伤和神经炎症生物标志物的验证早期历史，并对文献中与 TSPO 反应的细胞来源相关的有争议的主题进行了批判性分析。后者对于正确解释神经退行性和精神疾病中的 PET 研究非常重要。此外，本文还提出了一些尚未探索的解释来解释精神疾病中的新发现，并提出了新的方法来定量评估 TSPO 反应的神经胶质来源，以推动该领域的发展。
