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(1): 168-179, 2023 12.
Article
em En
| MEDLINE
| ID: mdl-37707571
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epilepsia do Lobo Temporal
Tipo de estudo:
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Eur J Nucl Med Mol Imaging
Ano de publicação:
2023
Tipo de documento:
Article