TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward.
TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward.
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DOI：
10.1016/j.pharmthera.2018.09.003
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发表时间：
2019-03
影响因子：
13.5
通讯作者：
Guilarte TR
中科院分区：
文献类型：
--
作者：
Guilarte TR
转运蛋白18 kDa（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使用在过去十年中呈指数级增长。用于TSPO正电子发射断层扫描（PET）成像的新放射性示踪剂的开发步伐非常快，现在已广泛描述了其在许多神经和精神疾病中的应用。这种快速的研究步伐和不断增加的新实验室进入该领域往往缺乏对该领域历史观点的认识，并引入了与TSPO对脑损伤和神经炎症反应的潜在神经生物学相关的教条但未经证实的事实。奇怪的是，虽然在神经退行性疾病和所有类型的CNS病理中脑TSPO水平增加，但在精神疾病如精神分裂症中的新观察结果是通过PET测量的脑TSPO水平降低。这一新发现的神经生物学基础目前尚不清楚，但使用多种实验方法进行严格的实验设计并仔细解释结果对于为这一新观察提供方法学和/或生物学基础至关重要。本文综述了验证TSPO作为脑损伤和神经炎症生物标志物的早期历史，并对文献中与TSPO反应的细胞来源相关的争议话题进行了批判性分析。后者是重要的，以提供正确的解释PET研究在神经退行性疾病和精神疾病。此外，这篇评论提出了一些有待探讨的解释精神疾病的新发现和新的方法来定量评估TSPO反应的胶质源，以推动该领域的发展。
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.
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影响因子：
3.2
作者：
Coughlin JM;Wang Y;Ma S;Yue C;Kim PK;Adams AV;Roosa HV;Gage KL;Stathis M;Rais R;Rojas C;McGlothan JL;Watkins CC;Sacktor N;Guilarte TR;Zhou Y;Sawa A;Slusher BS;Caffo B;Kassiou M;Endres CJ;Pomper MG
通讯作者：
Pomper MG
影响因子：
9.9
作者：
Banati, RB;Goerres, GW;Duncan, JS
通讯作者：
Duncan, JS
影响因子：
168.9
作者：
Cagnin, A;Brooks, DJ;Banati, RB
通讯作者：
Banati, RB
影响因子：
6.2
作者：
Biesmans, Steven;Acton, Paul D.;Nuydens, Rony
通讯作者：
Nuydens, Rony
影响因子：
4.7
作者：
BENAVIDES, J;QUARTERONET, D;LEFUR, G
通讯作者：
LEFUR, G