Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation.
Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation.
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DOI：
10.1016/j.bbi.2018.09.018
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Loggia ML
中科院分区：
文献类型：
--
作者：
Albrecht DS;Forsberg A;Sandström A;Bergan C;Kadetoff D;Protsenko E;Lampa J;Lee YC;Höglund CO;Catana C;Cervenka S;Akeju O;Lekander M;Cohen G;Halldin C;Taylor N;Kim M;Hooker JM;Edwards RR;Napadow V;Kosek E;Loggia ML
纤维肌痛（FM）是一种人们知之甚少的慢性疾病，其特征是广泛的肌肉骨骼疼痛、疲劳和认知困难。虽然越来越多的证据表明神经炎症的作用，但没有研究直接提供FM中脑胶质细胞激活的证据。在这项研究中，我们使用[11 C] PBR 28进行了正电子发射断层扫描（PET）研究，PBR 28与转运蛋白（TSPO）结合，TSPO是一种在活化的小胶质细胞和星形胶质细胞中上调的蛋白质。为了增强统计功效和可推广性，我们将两个独立机构（马萨诸塞州综合医院[MGH]和卡罗林斯卡医学院[KI]）独立收集的数据集合并。为了解开不同神经胶质细胞类型对FM的贡献，用[11 C]-L-丙炔苯丙胺-D2 PET在KI处扫描较小的样品，认为其主要反映星形胶质细胞（而不是小胶质细胞）信号。使用[11 C] PBR 28 PET检查了31例FM患者和27例健康对照（HC）。使用[11 C]-L-丙炔苯丙胺-D2 PET扫描11例FM患者和11例HC患者。根据[11 C] PBR 28数据计算通过枕叶皮质信号（SUVR）和分布容积（VT）标准化的标准化摄取值。使用λk3定量[11 C]-L-丙炔苯丙胺-D2。PET成像指标在各组之间进行比较，当各组之间存在差异时，对照临床变量进行比较。与HC相比，FM患者在[11 C] PBR 28 VT和SUVR中表现出广泛的皮质升高，并且没有降低，在额叶和顶叶的内侧壁和外侧壁中最明显。无区域显示[11 C]-L-丙炔苯丙胺-D2信号的显著组间差异，包括患者中显示[11 C] PBR 28信号升高的区域（p ≥0.53，未校正）。[11 C] PBR 28 VT和SUVR的升高在空间上都相关（即，在重叠的区域观察到了这种现象），在若干地区也观察到了这种现象的严重性。在探索性、未校正的分析中，FM患者的疲劳主观评分较高，与前部和后部中扣带皮层的[11 C] PBR 28 SUVR较高相关（p <0.03）。SUVR与任何其他临床变量均无显著相关性。我们的工作提供了第一个在体内的证据支持神经胶质细胞激活FM病理生理学的作用。鉴于[11 C] PBR 28信号的升高并不伴随[11 C]-L-丙炔苯丙胺-D2信号的增加，我们的数据表明，小胶质细胞而不是星形胶质细胞可能驱动这些区域的TSPO升高。虽然在FM患者中未发现[11 C]-L-丙炔苯丙胺-D2信号增加，但需要更大规模的研究来进一步评估可能的星形胶质细胞在FM中的作用。总的来说，我们的数据支持神经胶质调制作为FM的潜在治疗策略。
Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [11C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [11C]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [11C]PBR28 PET. 11 FM patients and 11 HC were scanned using [11C]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (VT) were computed from the [11C]PBR28 data. [11C]-L-deprenyl-D2 was quantified using λk3. PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [11C]PBR28 VT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [11C]-L-deprenyl-D2 signal, including those demonstrating elevated [11C]PBR28 signal in patients (p’s≥0.53, uncorrected). The elevations in [11C]PBR28 VT and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [11C]PBR28 SUVR in the anterior and posterior middle cingulate cortices (p’s<0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [11C]PBR28 signal were not also accompanied by increased [11C]-L-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [11C]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.
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影响因子：
3.2
作者：
Albrecht DS;MacKie PJ;Kareken DA;Hutchins GD;Chumin EJ;Christian BT;Yoder KK
通讯作者：
Yoder KK
DOI：
10.1007/s00259-015-3149-8
发表时间：
2016-01-01
影响因子：
9.1
作者：
Collste, K.;Forsberg, A.;Cervenka, S.
通讯作者：
Cervenka, S.
影响因子：
4.2
作者：
Gulyas, Balazs;Pavlova, Elena;Halldin, Christer
通讯作者：
Halldin, Christer
影响因子：
5.3
作者：
Abourbeh, Galith;Theze, Benoit;Boisgard, Raphael
通讯作者：
Boisgard, Raphael
影响因子：
2.7
作者：
Bäckryd E;Tanum L;Lind AL;Larsson A;Gordh T
通讯作者：
Gordh T