Hippocampal proteomic profile in temporal lobe epilepsy

Abstract

In this study we used proteomics approaches to obtain the protein profile of human epileptic hippocampi (N=6) and control hippocampi obtained from autopsy (N=6). We used two-dimensional gel electrophoresis (2-D) coupled to HPLC and Mass spectroscopy (MALDI-TOF) to identify proteins differentially expressed. Nine proteins were differentially expressed comparing the hippocampus of patients with the hippocampus of control. Proteins that were increased in the hippocampus of patients with TLE were: isoform 1 of serum albumin, HSP 70, dihydropyrimidinase-related protein 2, isoform 1 of myelin basic protein, proton ATPase catalytic subunit A, and dihydrolipoyllysine-residue acethyltransferase component of pyruvate dehydrogenase complex. The expression of isoform 3 of spectrin alpha chain (fodrin) was down-regulated while the proteins glutathione S-transferase P and the DJ-1 (PARK7) were detected only in the hippocampus of patients with TLE. Taken together, our results provide evidence supporting a direct link between metabolic disturb and oxidative damage related to pathophysiology of TLE. Besides, indicates biomarkers for further investigations as therapies targeted to epilepsy.

Granule Cell Dispersion in Human Temporal Lobe Epilepsy: Proteomics Investigation of Neurodevelopmental Migratory Pathways

“…These processes are active during neurodevelopment and in neurogenic niches in the adult mammalian brain (Lee et al, 2012;Frese et al, 2017). Our findings are consistent with previous human proteomic studies which have reported increased expression of DPYL2 (also known as collapsing response mediator protein 2, CRMP2), a cytoplasmic phosphoprotein that binds microtubules and promotes neurite outgrowth during neurogenesis and neuronal migration (Inagaki et al, 2001;Fukata et al, 2002), in the hippocampus of MTLE patients compared to controls (Persike et al, 2012(Persike et al, , 2018Keren-Aviram et al, 2018). The CRMP2 antagonist, lacosamide, is an antiepileptic drug often used in patients with drug-resistant epilepsy (Kelemen and Peter, 2010).…”

“…The differential expression of certain proteins in our study is generally consistent with findings from previous human MTLE studies. There is good agreement amongst human TLE proteomics studies that most proteins related to metabolism are significantly upregulated in epilepsy compared to archival normal brain hippocampal samples (Eun et al, 2004;Yang et al, 2006;Persike et al, 2012Persike et al, , 2018. This may be because the generation of epileptiform activity, or response to such activity, consumes a large amount of energy, and rapid glycolysis and oxidative phosphorylation are necessary to fulfill energy demands in the epileptic human brain (Kovac et al, 2017).…”

“…The proteome of the human hippocampus has been studied in normal (Edgar et al, 1999a;Föcking et al, 2012;Koopmans et al, 2018), and diseased post mortem human brains, including in the context of schizophrenia (Edgar et al, 1999b), Alzheimer's disease (Edgar et al, 1999b;Sultana et al, 2007;Begcevic et al, 2013;Hondius et al, 2016), and non-CNS malignancies (Yang et al, 2004a). In epilepsy, the proteomes of surgically-resected hippocampi from patients with refractory TLE (Czech et al, 2004;Yang et al, 2004bYang et al, , 2006Persike et al, 2012Persike et al, , 2018Mériaux et al, 2014) or temporal cortex (Eun et al, 2004;He et al, 2006;Keren-Aviram et al, 2018) have been studied. Most of these past studies investigated the whole hippocampus rather than specific hippocampal subregions, and information about structural hippocampal pathology was not disclosed in three studies (Czech et al, 2004;Persike et al, 2012Persike et al, , 2018.…”

“…In epilepsy, the proteomes of surgically-resected hippocampi from patients with refractory TLE (Czech et al, 2004;Yang et al, 2004bYang et al, , 2006Persike et al, 2012Persike et al, , 2018Mériaux et al, 2014) or temporal cortex (Eun et al, 2004;He et al, 2006;Keren-Aviram et al, 2018) have been studied. Most of these past studies investigated the whole hippocampus rather than specific hippocampal subregions, and information about structural hippocampal pathology was not disclosed in three studies (Czech et al, 2004;Persike et al, 2012Persike et al, , 2018. None of the previous human proteomic studies discussed GCD in their samples.…”

Epilepsia do lobo temporal: mecanismos e perspectivas

“…Nosso grupo também tem trazido contribuição para a área da proteômica e epilepsia. Recentemente, Persike et al (2012) mostraram que o hipocampo de paciente com epilepsia do lobo temporal possui menor número de spots do que o tecido controle, ou seja, menor expressão proteica (Comitê de Ética n.1692/05). De um total de 16 proteínas diferencialmente expressas entre os grupos de pacientes epilépticos e controle, apenas nove puderam ser identificadas.…”