TY - JOUR
T1 - Toward molecular phenotyping of temporal lobe epilepsy by spatial omics
AU - Vermeulen, Isabeau
AU - Mohren, Ronny
AU - Neusinger, Micca
AU - Dancker, Tobias A.
AU - Vandenbosch, Michiel
AU - Beckervordersandforth, Jan
AU - Balluff, Benjamin
AU - van der Hel, Rianna P.
AU - Schijns, Olaf E. M. G.
AU - Hoogland, Govert
AU - Rijkers, Kim
AU - Cillero-Pastor, Berta
AU - Grp, ACE Epilepsy Surg
PY - 2025/3/20
Y1 - 2025/3/20
N2 - ObjectiveIn temporal lobe epilepsy (TLE), detection of the epileptogenic zone predicts a good surgical outcome. When submitted to 18F-fluorodeoxyglucose positron emission tomography (PET), some patients display lateralized, focal hypometabolism in the temporal lobe (PET+), whereas others appear normometabolic (PET-). However, the mechanism behind this metabolic difference remains unclear. This study aimed to identify differential molecular mechanisms in these patient subtypes.MethodsNeocortical and hippocampal biopsies of TLE patients (n = 3 PET+, n = 3 PET-) and nonepileptic postmortem controls (n = 3) were analyzed for lipid distribution using mass spectrometry imaging (MSI). Laser capture microdissection of the neocortical gray matter and hippocampal cornu ammonis and dentate gyrus was guided by MSI-derived lipid profiles and histological annotations. Dissected areas were then subjected to liquid chromatography- tandem mass spectrometry-based label-free quantitative proteomic analysis.ResultsMSI showed distinct lipid profiles, namely, phosphatidylserines were more abundant in PET+ samples in both the neocortex and hippocampus. Proteomic analysis showed significant differences between TLE and nonepileptic postmortem controls involving pathways in neuron excitability and neurotransmitter transporters, which were upregulated in TLE. Compared to PET-, all PET+ specimens displayed significantly dysregulated calcium signaling. Additionally, the neocortex of PET+ patients showed a shift from mitochondrial to cytosolic (cytoplasm of the cell) processes, whereas the hippocampus was characterized by a disruption of glycosylation and polyamine metabolism.SignificanceThe applied spatial omics approach demonstrated localized molecular differences between metabolic subtypes of TLE patients. These findings may further specify these TLE subtypes and provide leads for targeted treatment.
AB - ObjectiveIn temporal lobe epilepsy (TLE), detection of the epileptogenic zone predicts a good surgical outcome. When submitted to 18F-fluorodeoxyglucose positron emission tomography (PET), some patients display lateralized, focal hypometabolism in the temporal lobe (PET+), whereas others appear normometabolic (PET-). However, the mechanism behind this metabolic difference remains unclear. This study aimed to identify differential molecular mechanisms in these patient subtypes.MethodsNeocortical and hippocampal biopsies of TLE patients (n = 3 PET+, n = 3 PET-) and nonepileptic postmortem controls (n = 3) were analyzed for lipid distribution using mass spectrometry imaging (MSI). Laser capture microdissection of the neocortical gray matter and hippocampal cornu ammonis and dentate gyrus was guided by MSI-derived lipid profiles and histological annotations. Dissected areas were then subjected to liquid chromatography- tandem mass spectrometry-based label-free quantitative proteomic analysis.ResultsMSI showed distinct lipid profiles, namely, phosphatidylserines were more abundant in PET+ samples in both the neocortex and hippocampus. Proteomic analysis showed significant differences between TLE and nonepileptic postmortem controls involving pathways in neuron excitability and neurotransmitter transporters, which were upregulated in TLE. Compared to PET-, all PET+ specimens displayed significantly dysregulated calcium signaling. Additionally, the neocortex of PET+ patients showed a shift from mitochondrial to cytosolic (cytoplasm of the cell) processes, whereas the hippocampus was characterized by a disruption of glycosylation and polyamine metabolism.SignificanceThe applied spatial omics approach demonstrated localized molecular differences between metabolic subtypes of TLE patients. These findings may further specify these TLE subtypes and provide leads for targeted treatment.
KW - Maldi-msi
KW - Lipidomics
KW - Metabolism
KW - Proteomics
KW - Temporal lobe epilepsy
U2 - 10.1111/epi.18366
DO - 10.1111/epi.18366
M3 - Article
C2 - 40110881
SN - 0013-9580
JO - Epilepsia
JF - Epilepsia
ER -