The Clinical Hospital of Chengdu Brain Science Institute, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
MOE Key Lab for Neuroinformation, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu, China.
Commun Biol. 2024 Aug 20;7(1):1019. doi: 10.1038/s42003-024-06726-0.
Genetic generalized epilepsies (GGE) exhibit widespread morphometric alterations in the subcortical structures. Subcortical structures are essential for understanding GGE pathophysiology, but their fine-grained morphological diversity has yet to be comprehensively investigated. Furthermore, the relationships between macroscale morphological disturbances and microscale molecular chemoarchitectures are unclear. High-resolution structural images were acquired from patients with GGE (n = 97) and sex- and age-matched healthy controls (HCs, n = 184). Individual measurements of surface shape features (thickness and surface area) of seven bilateral subcortical structures were quantified. The patients and HCs were then compared vertex-wise, and shape anomalies were co-located with brain neurotransmitter profiles. We found widespread morphological alterations in GGE and prominent disruptions in the thalamus, putamen, and hippocampus. Shape area dilations were observed in the bilateral ventral, medial, and right dorsal thalamus, as well as the bilateral lateral putamen. We found that the shape area deviation pattern was spatially correlated with the norepinephrine transporter and nicotinic acetylcholine (Ach) receptor (αβ) profiles, but a distinct association was seen in the muscarinic Ach receptor (M). The findings provided a comprehensive picture of subcortical morphological disruptions in GGE, and further characterized the associated molecular mechanisms. This information may increase our understanding of the pathophysiology of GGE.
遗传全面性癫痫（GGE）在皮质下结构中表现出广泛的形态改变。皮质下结构对于理解 GGE 的病理生理学至关重要，但它们的细微形态多样性尚未得到全面研究。此外，宏观形态障碍与微观分子化学构筑之间的关系尚不清楚。从 GGE 患者（n=97）和性别及年龄匹配的健康对照组（HC，n=184）中获取高分辨率结构图像。定量了七个双侧皮质下结构的表面形状特征（厚度和表面积）的个体测量值。然后对患者和 HC 进行了顶点比较，并将形态异常与大脑神经递质分布进行了对比。我们发现 GGE 存在广泛的形态改变，并且丘脑、壳核和海马体明显受到破坏。双侧腹侧、内侧和右侧背侧丘脑以及双侧外侧壳核均观察到形状面积扩张。我们发现，形状面积偏差模式与去甲肾上腺素转运体和烟碱型乙酰胆碱（Ach）受体（αβ）分布呈空间相关，但在毒蕈碱型 Ach 受体（M）中则存在明显的相关性。这些发现提供了 GGE 皮质下形态破坏的全面图景，并进一步描述了相关的分子机制。这些信息可能会增加我们对 GGE 病理生理学的理解。
