Metabolomic characterization of human hippocampus from drug-resistant epilepsy with mesial temporal seizure
Author(s)
Date
2018-03Source Title
Epilepsia
Print ISSN
0013-9580
Electronic ISSN
1528-1167
Publisher
Wiley-Blackwell Publishing
Volume
59
Issue
3
Pages
607 - 616
Language
English
Type
ArticleItem Usage Stats
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Abstract
Within a complex systems biology perspective, we wished to assess
whether hippocampi with established neuropathological features have distinct metabolome.
Apparently normal hippocampi with no signs of sclerosis (noHS), were
compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus
metabolome from patients with epilepsy-associated neuroepithelial
tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial
tumors (DNTs), was also compared to noHS epileptiform tissue.
Methods: All patients underwent standardized temporal lobectomy. We applied
1H high-resolution magic angle spinning nuclear magnetic resonance (HRMAS
NMR) spectroscopy to 48 resected human hippocampi. NMR spectra allowed
quantification of 21 metabolites. Data were analyzed using multivariate analysis
based on mutual information.
Results: Clear distinct metabolomic profiles were observed between all studied
groups. Sixteen and 18 expected metabolite levels out of 21 were significantly
different for HS1 and HS2, respectively, when compared to noHS. Distinct concentration
variations for glutamine, glutamate, and N-acetylaspartate (NAA) were
observed between HS1 and HS2. Hippocampi from GG and DNT patients showed
7 and 11 significant differences in metabolite concentrations when compared to
the same group, respectively. GG and DNT had a clear distinct metabolomic profile,
notably regarding choline compounds, glutamine, glutamate, aspartate, and
taurine. Lactate and acetate underwent similar variations in both groups.
Significance: HRMAS NMR metabolomic analysis was able to disentangle metabolic
profiles between HS, noHS, and epileptic hippocampi associated with
EANT. HRMAS NMR metabolomic analysis may contribute to a better identification
of abnormal biochemical processes and neuropathogenic combinations underlying
mesial temporal lobe epilepsy.
Keywords
Hippocampal sclerosisHRMAS NMR
Long-term epilepsy-associated tumor
Mesial temporal lobe epilepsy
Metabolomics