White matter deficits in cocaine use disorder: convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomic analysis.
White matter deficits in cocaine use disorder: convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomic analysis.
复制标题
DOI：
10.1038/s41398-021-01367-x
复制
发表时间：
2021-04-29
影响因子：
6.8
通讯作者：
Grassi-Oliveira R
中科院分区：
文献类型：
--
作者：
Tondo LP;Viola TW;Fries GR;Kluwe-Schiavon B;Rothmann LM;Cupertino R;Ferreira P;Franco AR;Lane SD;Stertz L;Zhao Z;Hu R;Meyer T;Schmitz JM;Walss-Bass C;Grassi-Oliveira R
可卡因使用障碍（CUD）患者的白色物质（WM）异常已被研究;然而，报告的对人脑的影响是异质性的，大多数结果是从男性参与者中获得的。此外，生物学数据支持的成像结果和揭示潜在的机制慢性可卡因使用（CU）对WM的神经毒性作用在很大程度上限于动物研究。为了评估CU在WM中的神经毒性作用，我们对男性和女性可卡因使用者（n = 75）和健康对照（HC）（n = 58）进行了体内扩散张量成像评估。此外，我们进行了离体大规模的蛋白质组学分析，使用液相色谱-串联质谱法在死后的CUD（n = 8）和HC（n = 12）患者的大脑。与HC组相比，CUD组显示整体各向异性分数（FA）显著降低（p < 0.001），整体平均值（MD）和径向扩散（RD）增加（均p < 0.001）。结果显示，FA，RD，MD改变在CUD组广泛沿着主要WM束，分析后，使用基于道的特殊统计方法。总FA与CU年数（p = 0.0421）和女性性别（p < 0.001）呈负相关，但与酒精或尼古丁使用年数无关。关于连接左至右前额叶皮质的纤维，Brodmann 9区（BA 9），与HC组相比，CUD组表现出较低的FA（p = 0.006）和较高的RD（p < 0.001）值。还观察到CU在生命中的持续时间与该道中的FA值之间存在负相关（p = 0.019）。BA 9的蛋白质组学分析发现可卡因使用者和对照组之间有11种蛋白质差异表达。其中，与髓鞘形成和神经炎症相关的蛋白质。总之，我们证明收敛的证据，从体内扩散张量成像和离体蛋白质组学分析WM中断CUD。
White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.
登录
查看更多内容
影响因子：
5.4
作者：
Castillo, Eliseo F.;Zheng, Handong;Van Cabanlong, Christian;Dong, Fei;Luo, Yan;Yang, Yi;Liu, Meilian;Kao, Winston W. -Y.;Yang, Xuexian O.
通讯作者：
Yang, Xuexian O.
影响因子：
2.7
作者：
Elman, I;Karlsgodt, KH;Gastfriend, DR
通讯作者：
Gastfriend, DR
影响因子：
5.7
作者：
Bach, Michael;Laun, Frederik B.;Maier-Hein, Klaus H.
通讯作者：
Maier-Hein, Klaus H.
影响因子：
25.8
作者：
Grant, Bridget F.;Saha, Tulshi D.;Ruan, W. June;Goldstein, Rise B.;Chou, S. Patricia;Jung, Jeesun;Zhang, Haitao;Smith, Sharon M.;Pickering, Roger P.;Huang, Boji;Hasin, Deborah S.
通讯作者：
Hasin, Deborah S.
影响因子：
2.5
作者：
Baliyan V;Das CJ;Sharma R;Gupta AK
通讯作者：
Gupta AK