Alterations of brain microstructures in a mouse model of prenatal opioid exposure detected by diffusion MRI.
Alterations of brain microstructures in a mouse model of prenatal opioid exposure detected by diffusion MRI.
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DOI：
10.1038/s41598-022-21416-9
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发表时间：
2022-10-12
影响因子：
4.6
通讯作者：
Wu, Yu-Chien
中科院分区：
文献类型：
--
作者：
Grecco, Gregory G.;Shahid, Syed Salman;Atwood, Brady K.;Wu, Yu-Chien
孕妇中阿片类药物的使用越来越多，这加剧了产前阿片类药物暴露婴儿的危机。大量的研究一直致力于研究这些婴儿在新生儿期阿片类药物戒断的管理，但较少的实质性工作探讨了产前阿片类药物暴露对神经发育的长期影响。本研究利用产前美沙酮暴露（PME）小鼠模型，探讨PME小鼠与产前生理盐水暴露（PSE）小鼠脑组织微结构的差异。在9.4特斯拉小动物扫描仪上使用高分辨率体内扩散磁共振成像对患有PME（n = 15）或PSE（n = 15）的8周龄雄性后代的大脑进行成像。采用扩散张量成像（DTI）和宾汉神经突方向弥散和密度成像（Bingham-NODDI）对脑显微结构进行表征。使用计算的微观结构参数图进行基于体素的分析（VXI）。与PSE相比，在几个皮质和皮质下区域，MRI显示了分数各向异性（FA）、平均扩散率（MD）、轴向扩散率（AD）、径向扩散率（RD）、方向弥散指数（ODI）和弥散各向异性指数（DAI）的双侧显著（p < 0.05）变化。特别是，在PME后代，海马，杏仁核，丘脑，隔核，背侧纹状体和丘脑背侧核的FA，MD和AD显着较高。这些DTI为基础的结果表明，广泛的双边微结构的改变，在PME后代的皮质和皮质下区域。与DTI中的观察结果一致，Bingham-NODDI衍生的ODI在海马、背侧纹状体和皮质内的PME后代中表现出显著减少。基于NODDI的结果进一步表明，在多个皮层和皮层下区域的PME后代的树突状分支减少。据我们所知，这是第一个研究产前阿片类药物暴露检查体内微观结构组织。我们的研究结果表明，皮质和皮质下区域的微结构复杂性持续到成年早期，这可能会干扰产前阿片类药物暴露个体的关键神经发育过程。
Growing opioid use among pregnant women is fueling a crisis of infants born with prenatal opioid exposure. A large body of research has been devoted to studying the management of opioid withdrawal during the neonatal period in these infants, but less substantive work has explored the long-term impact of prenatal opioid exposure on neurodevelopment. Using a translationally relevant mouse model of prenatal methadone exposure (PME), the aim of the study is to investigate the cerebral microstructural differences between the mice with PME and prenatal saline exposure (PSE). The brains of eight-week-old male offspring with either PME (n = 15) or PSE (n = 15) were imaged using high resolution in-vivo diffusion magnetic resonance imaging on a 9.4 Tesla small animal scanner. Brain microstructure was characterized using diffusion tensor imaging (DTI) and Bingham neurite orientation dispersion and density imaging (Bingham-NODDI). Voxel-based analysis (VBA) was performed using the calculated microstructural parametric maps. The VBA showed significant (p < 0.05) bilateral alterations in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), orientation dispersion index (ODI) and dispersion anisotropy index (DAI) across several cortical and subcortical regions, compared to PSE. Particularly, in PME offspring, FA, MD and AD were significantly higher in the hippocampus, dorsal amygdala, thalamus, septal nuclei, dorsal striatum and nucleus accumbens. These DTI-based results suggest widespread bilateral microstructural alterations across cortical and subcortical regions in PME offspring. Consistent with the observations in DTI, Bingham-NODDI derived ODI exhibited significant reduction in PME offspring within the hippocampus, dorsal striatum and cortex. NODDI-based results further suggest reduction in dendritic arborization in PME offspring across multiple cortical and subcortical regions. To our best knowledge, this is the first study of prenatal opioid exposure to examine microstructural organization in vivo. Our findings demonstrate perturbed microstructural complexity in cortical and subcortical regions persisting into early adulthood which could interfere with critical neurodevelopmental processes in individuals with prenatal opioid exposure.
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