[11C]PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.,Molecular Psychiatry

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[11C]PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2020-02-19 , DOI: 10.1038/s41380-020-0682-z
N R Zürcher _{1,

2} , M L Loggia _{1,

2} , J E Mullett ₃ , C Tseng _{1,

2} , A Bhanot ₁ , L Richey ₁ , B G Hightower ₁ , C Wu ₁ , A J Parmar ₁ , R I Butterfield ₁ , J M Dubois _{1,

2} , D B Chonde _{1,

2} , D Izquierdo-Garcia _{1,

2} , H Y Wey _{1,

2} , C Catana _{1,

2} , N Hadjikhani _{1,

2,

4} , C J McDougle _{2,

3} , J M Hooker _{1,

2}

Affiliation

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.

中文翻译：

[11C]PBR28 MR-PET 成像显示患有自闭症谱系障碍的年轻成年男性易位蛋白 (TSPO) 的区域脑表达较低。

神经免疫和线粒体功能障碍的机制已多次与自闭症谱系障碍（ASD）有关。为了检查 ASD 个体的这些机制，我们测量了 18 kDa 易位蛋白 (TSPO) 的体内表达，TSPO 是一种在线粒体膜上表达的激活的神经胶质标记物。参与者使用第二代 TSPO 放射性示踪剂 [11C]PBR28 在同步磁共振正电子发射断层扫描 (MR-PET) 扫描仪上进行扫描。通过将 15 名患有 ASD 的年轻成年男性与 18 名年龄和性别匹配的对照组的 TSPO 进行比较，我们发现患有 ASD 的个体在多个大脑区域表现出较低的局部 TSPO 表达，包括双侧岛叶皮层、双侧楔前叶/后扣带皮层和双侧颞回、角回和边缘上回，此前在功能磁共振成像研究中已发现这些区域与自闭症有关。与对照组相比，自闭症谱系障碍组中没有大脑区域表现出更高的区域 TSPO 表达。一部分参与者在平均扫描间隔为 3.6 个月后接受了第二次 MR-PET 扫描，我们确定这段时间内 TSPO 的表达是稳定且可复制的。此外，体素分析证实了 ASD 中较晚时间点的区域 TSPO 表达较低。ASD 中较低的 TSPO 表达可能反映了神经免疫过程的异常或线粒体功能障碍。

更新日期：2020-02-19

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