Transcriptionally downregulated GABAergic genes associated with synaptic density network dysfunction in temporal lobe epilepsy.
Purpose: Temporal lobe epilepsy (TLE) is a brain network disorder closely associated with synaptic loss and has a genetic basis. However, the in vivo whole-brain synaptic changes at the network-level and the underlying gene expression patterns in patients with TLE remain unclear. Methods: In this st...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 52; no. 6; pp. 1970 - 1989 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
May2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=184671072&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 184671072 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: May2025 vid: 52 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 184671072 182090240 10.1007/s00259-024-07054-5 184671072 ppf: 1970 ppct: 19 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Transcriptionally downregulated GABAergic genes associated with synaptic density network dysfunction in temporal lobe epilepsy. aug: au: Li, Rong Xiao, Ling Han, Honghao Long, Hongyu Liao, Wei Yang, Zhenzhe Zhu, Haoyue Wang, Xuyang Zou, Ting Huang, Yongwen Biswal, Bharat B. Zhou, Ming Li, Jian Li, Yulai Rominger, Axel Shi, Kuangyu Chen, Huafu Tang, Yongxiang Feng, Li Hu, Shuo affil: https://ror.org/04qr3zq92 The Clinical Hospital of Chengdu Brain Science Institute, School of Life Science and Technology, University of Electronic Science and Technology of China, 611731, Chengdu, P.R. China sug: ab: Purpose: Temporal lobe epilepsy (TLE) is a brain network disorder closely associated with synaptic loss and has a genetic basis. However, the in vivo whole-brain synaptic changes at the network-level and the underlying gene expression patterns in patients with TLE remain unclear. Methods: In this study, we utilized a positron emission tomography with the synaptic vesicle glycoprotein 2 A radioligand [18F]SynVesT-1 cohort and two independent transcriptome datasets to investigate the topological properties of the synaptic density similarity network (SDSN) in TLE and its correlation with significantly dysregulated risk genes. Results: We observed an overall decrease in strength, reduced clustering coefficient, and increased path length of SDSN in TLE, suggesting a loss of connectivity that is accompanied by network reorganization. These changes were predominantly distributed in the temporo-limbic circuit and fronto-parietal networks. Moreover, connectivity changes in SDSN were found to be spatially correlated with the brain-wide expression of TLE risk genes, and the transcriptional correlate of SDSN changes showed a significant relationship with gene dysregulation. In particular, we identified a total of 183 downregulated genes that were functionally enriched for synaptic transmission pathways, forming a highly connected genetic interaction network. Within this set of genes, GABAergic genes such as RBFOX1 play a central role. Discussion: Our study provides the first evidence that the spatial expression patterns of downregulated risk genes underlie in vivo synaptic density network dysfunction in TLE. These imaging-transcriptomic findings have the potential to guide the development of molecular and genetic network-based therapeutic approaches for TLE. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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