Department of Biophysics and Nuclear Medicine, University Hospitals of Strasbourg, Strasbourg, France.
Department of Pharmacy, University Hospitals of Strasbourg, Strasbourg, France.
Epilepsia. 2018 Mar;59(3):607-616. doi: 10.1111/epi.14000. Epub 2018 Jan 17.
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.
All patients underwent standardized temporal lobectomy. We applied H 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.
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.
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.
从复杂系统生物学的角度出发，我们希望评估是否存在具有既定神经病理学特征的海马体具有独特的代谢组。将无硬化迹象的明显正常海马体（noHS）与海马硬化 1 型（HS1）和/或 2 型（HS2）进行比较。还将癫痫相关神经上皮肿瘤（EANT）患者的海马代谢组，即神经节细胞瘤（GG）和发育不良性神经上皮肿瘤（DNT），与 noHS 癫痫样组织进行比较。
所有患者均接受了标准的颞叶切除术。我们应用高分辨率魔角旋转核磁共振（HRMAS NMR）光谱学对 48 例切除的人类海马体进行了分析。NMR 光谱允许定量分析 21 种代谢物。使用基于互信息的多变量分析对数据进行分析。
在所有研究组之间观察到明显不同的代谢组学特征。与 noHS 相比，HS1 和 HS2 分别有 16 和 18 种预期代谢物水平有显著差异。在 HS1 和 HS2 之间观察到谷氨酰胺、谷氨酸和 N-乙酰天冬氨酸（NAA）的浓度变化。与同一组相比，GG 和 DNT 患者的海马代谢物浓度分别有 7 和 11 种差异。GG 和 DNT 的代谢组学特征明显不同，尤其是在胆碱化合物、谷氨酰胺、谷氨酸、天冬氨酸和牛磺酸方面。两组的乳酸和乙酸都有类似的变化。
HRMAS NMR 代谢组学分析能够区分 HS、noHS 和与 EANT 相关的癫痫海马体的代谢谱。HRMAS NMR 代谢组学分析可能有助于更好地识别内侧颞叶癫痫潜在的异常生化过程和神经病理组合。
