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Differences in whole-brain metabolism are associated with the expression of genes related to neurovascular unit integrity and synaptic plasticity in temporal lobe epilepsy

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Abstract

Purpose

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.

Methods

In this retrospective study, 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]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.

Results

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.

Discussion

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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Code is available from the corresponding author on reasonable request.

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Acknowledgements

We extend our deepest appreciation to the research participants and their families.

Funding

The study was funded by the National Key Research and Development Program of China (grant 2022YFC2503804), the National Natural Science Foundation of China (grant 82272045, 91859207, 82271503, 82071461, and 81771873), the Science and Technology Innovation Program of Hunan Province (grant 2021RC4056), the clinical research foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA) (grant 2020LNJJ01), the National Science Foundation of Hunan Province (grant 2020JJ5922 and 2021JJ31060), and the Key Program of Ministry of Industry and Information Technology of China (CEIEC-2022-ZM02-0219).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, Hunan, China

    Ling Xiao, Yongxiang Tang, Jian Li & Shuo Hu

  2. 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

    Chijun Deng & Rong Li

  3. Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, Hunan, China

    Haoyue Zhu, Danni Guo, Hongyu Long & Li Feng

  4. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhiquan Yang

  5. Department of Neurology, Xiangya Hospital, Central South University (Jiangxi Branch), Nanchang, Jiangxi, China

    Li Feng

  6. National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Li Feng & Shuo Hu

  7. Key Laboratory of Biological Nanotechnology of National Health Commission, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Shuo Hu

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  1. Ling Xiao
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  8. Zhiquan Yang
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  9. Hongyu Long
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  10. Li Feng
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  11. Shuo Hu
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Ling Xiao, Yongxiang Tang, Chijun Deng, Rong Li, Haoyue Zhu, Danni Guo, and Jian Li. Zhiquan Yang performed the epilepsy surgery and provided prognostic information. The first draft of the manuscript was written by Ling Xiao and Yongxiang Tang. Li Feng, Hongyu Long, and Shuo Hu revised the work critically for important intellectual content. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hongyu Long, Li Feng or Shuo Hu.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Xiangya Hospital, Central South University.

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Ling Xiao and Yongxiang Tang contributed equally to this work as co-first authors.

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Xiao, L., Tang, Y., Deng, C. et al. Differences in whole-brain metabolism are associated with the expression of genes related to neurovascular unit integrity and synaptic plasticity in temporal lobe epilepsy. Eur J Nucl Med Mol Imaging 51, 168–179 (2023). https://doi.org/10.1007/s00259-023-06433-8

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