Department of Nuclear Medicine, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, Hunan, China.
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Eur J Nucl Med Mol Imaging. 2023 Dec;51(1):168-179. doi: 10.1007/s00259-023-06433-8. Epub 2023 Sep 14.
Temporal lobe epilepsy (TLE) is a common, polygenic epilepsy syndrome that involves glucose hypometabolism in the epileptogenic zone. However, the transcriptional and cellular signatures underlying the metabolism in TLE remain unclear.
In this retrospective study, 2-[F]-fluoro-2-deoxy-D-glucose ([F]FDG) positron emission tomography (PET) scans of TLE patients (n = 104) who underwent anterior temporal lobectomy were consecutively collected between 2016 and 2021. The transcriptional profiles of TLE risk genes across the brain were identified by the gene expression analyses from six TLE patients and twelve postmortem donors (six from the Allen Human Brain Atlas). Integrating the neuroimaging and transcriptomic data, we examined the relationship between the expression of TLE-associated genes and metabolic alterations in TLE. Furthermore, we performed functional enrichment analyses of the genes with higher weight in partial least squares regression using Metascape.
A total of 104 patients with TLE (mean age 29 ± 9 years, 50% male) and 30 healthy controls (HCs) (mean age 31 ± 6 years, 53% male) were enrolled. Compared to that of HCs, patients with TLE showed hypometabolism in the temporal lobes and adjacent structures but hypermetabolism in the thalamus and basal ganglia. The cortical map of inter-group differences in cerebral metabolism was spatially correlated with the expression of a weighted combination of genes enriched in ontology terms and pathways related to neurovascular unit (NVU) integrity and synaptic plasticity.
Our findings, combined with the analysis of neuroimaging and transcriptional data, suggest that genes related to NVU integrity and synaptic plasticity may drive alterations to brain metabolism that mediate the genetic risk of TLE.
颞叶癫痫（TLE）是一种常见的多基因癫痫综合征，涉及致痫区的葡萄糖代谢低下。然而，TLE 代谢的转录和细胞特征尚不清楚。
在这项回顾性研究中，连续收集了 2016 年至 2021 年间接受前颞叶切除术的 104 例 TLE 患者的 2-[F]-氟-2-脱氧-D-葡萄糖 ([F]FDG) 正电子发射断层扫描（PET）扫描。通过对 6 例 TLE 患者和 12 例死后供体（Allen 人类大脑图谱中的 6 例）的基因表达分析，确定了 TLE 风险基因在整个大脑中的转录谱。整合神经影像学和转录组数据，我们研究了 TLE 相关基因的表达与 TLE 代谢改变之间的关系。此外，我们使用 Metascape 对偏最小二乘回归中权重较高的基因进行了功能富集分析。
共纳入 104 例 TLE 患者（平均年龄 29±9 岁，50%为男性）和 30 例健康对照者（HCs）（平均年龄 31±6 岁，53%为男性）。与 HCs 相比，TLE 患者的颞叶及相邻结构代谢低下，而丘脑和基底节代谢亢进。脑代谢组间差异的皮质图谱在空间上与本体论术语和与神经血管单元（NVU）完整性和突触可塑性相关的途径富集的基因的加权组合的表达相关。
我们的研究结果，结合神经影像学和转录组数据分析，表明与 NVU 完整性和突触可塑性相关的基因可能会导致大脑代谢改变，从而介导 TLE 的遗传风险。
