Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases.
Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases.
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DOI：
10.1038/s41467-023-40937-z
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发表时间：
2023-08-28
影响因子：
16.6
通讯作者：
Owen, David R.
中科院分区：
文献类型：
--
作者：
Nutma, Erik;Fancy, Nurun;Weinert, Maria;Tsartsalis, Stergios;Marzin, Manuel C.;Muirhead, Robert C. J.;Falk, Irene;Breur, Marjolein;de Bruin, Joy;Hollaus, David;Pieterman, Robin;Anink, Jasper;Story, David;Chandran, Siddharthan;Tang, Jiabin;Trolese, Maria C.;Saito, Takashi;Saido, Takaomi C.;Wiltshire, Katharine H.;Beltran-Lobo, Paula;Phillips, Alexandra;Antel, Jack;Healy, Luke;Dorion, Marie-France;Galloway, Dylan A.;Benoit, Rochelle Y.;Amosse, Quentin;Ceyzeriat, Kelly;Badina, Aurelien M.;Koevari, Enikoe;Bendotti, Caterina;Aronica, Eleonora;Radulescu, Carola I.;Wong, Jia Hui;Barron, Anna M.;Smith, Amy M.;Barnes, Samuel J.;Hampton, David W.;van der Valk, Paul;Jacobson, Steven;Howell, Owain W.;Baker, David;Kipp, Markus;Kaddatz, Hannes;Tournier, Benjamin B.;Millet, Philippe;Matthews, Paul M.;Moore, Craig S.;Amor, Sandra;Owen, David R.
小胶质细胞活化在神经炎性和神经退行性疾病中起核心作用。靶向18 kDa转运蛋白（TSPO）的正电子发射断层扫描（PET）被广泛用于体内炎症定位，但其定量解释仍不确定。我们表明，TSPO表达增加激活小胶质细胞在小鼠脑疾病模型，但不改变在非人灵长类动物疾病模型或在常见的神经退行性和神经炎性人类疾病。我们描述了TSPO基因启动子的遗传差异，这与以下假设一致：TSPO在活化的骨髓细胞中的表达增加取决于转录因子AP 1，并且是鼠总科中啮齿动物物种的一个子集所独有的。最后，我们确定LCP 2和TFEC作为人类小胶质细胞活化的潜在标志物。这些数据强调了TSPO在人类骨髓细胞中的表达与小鼠中的不同现象有关，并且人类中的TSPO-PET信号反映了炎症细胞的密度而不是活化状态。TSPO PET成像广泛用于量化小胶质细胞活化。在这里，作者表明TSPO表达在活化的啮齿动物中增加，但在人类小胶质细胞中没有增加，这意味着在人类中TSPO与小胶质细胞密度有关，而不是与活化状态有关。
Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state. TSPO PET imaging is widely used to quantify microglial activation. Here, the authors show that TSPO expression increases in activated rodent but not human microglia, implying that in humans TSPO informs on microglial density rather than activation status.
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