Altered vesicular glutamate transporter expression in human temporal lobe epilepsy with hippocampal sclerosis

Abstract

Link to publication Citation for published version (APA):Van Liefferinge, J., Jensen, C. J., Albertini, G., Bentea, E., Demuyser, T., Merckx, E., ... Massie, A. (2015). Altered vesicular glutamate transporter expression in human temporal lobe epilepsy with hippocampal sclerosis. Neuroscience Letters, 590, 184-188. DOI: 10.1016/j.neulet.2015 General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 13 May 2018Neuroscience Letters 590 (2015) [184][185][186][187][188] Contents lists available at ScienceDirect Neuroscience Letters j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / n e u l e t h i g h l i g h t s• VGLUTs mRNA remains unaffected in human sclerotic hippocampus ILAE type1.• Unaltered total VGLUT1 protein level in hippocampus of human TLE with HS ILAE type1.• Decreased VGLUT2 protein expression in hippocampus of human TLE with HS ILAE type1.• Increased VGLUT3 protein expression in hippocampus of human TLE with HS ILAE type1. a b s t r a c t Vesicular glutamate transporters (VGLUTs) are responsible for loading glutamate into synaptic vesicles. Altered VGLUT protein expression has been suggested to affect quantal size and glutamate release under both physiological and pathological conditions. In this study, we investigated mRNA and protein expression levels of the three VGLUT subtypes in hippocampal tissue of patients suffering from temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS), International League Against Epilepsy type1 (ILAE type1) compared to autopsy controls, using quantitative polymerase chain reaction and semi-quantitative western blotting. mRNA expression levels of the VGLUTs are unaffected in hippocampal epileptic tissue compared to autopsy controls. At the protein level, VGLUT1 expression remains unaltered, while VGLUT2 is significantly decreased and VGLUT3 protein is significantly increased in hippocampal biopsies from TLE patients compared to controls. Our findings at the protein level can be explained by previously described histopathological changes observed in HS. a r t i c l e i n f oAlthough VGLUTs have been repeatedly investigated in distinct rodent epilepsy models, their expression levels were hitherto not fully unraveled in the most difficult-to-treat form of epilepsy: TLE with HS ILAE t...

Proteomics for Studying the Effects of Ketogenic Diet Against Lithium Chloride/Pilocarpine Induced Epilepsy in Rats

“…Solute carrier family 17 (Sodium-dependent inorganic phosphate cotransporter), member 6, also known as vesicular glutamate transporter 2 (VGLUT2, encoded by Slc17a6) is a low affinity transporter of glutamate from the cytoplasm into synaptic vesicles ( Bellocchio et al, 2000 ). Expression is lower in the hippocampus of patients with intractable epilepsy and hippocampal sclerosis ( Van Liefferinge et al, 2015 ), consistent with findings of reduced abundance in the SE group. Lobo et al (2011) found that high glutamic acid exposure reduced VGLUT2 expression by hippocampal neurons, resulting in substantial excitotoxicity.…”

“…Alternatively, each of these pathogenic processes was reversed by KD. In addition, KD upregulated the abundance of solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter) member 6 and complexin 3, both of which are neuroprotective ( Ono et al, 1998 ; Van Liefferinge et al, 2015 ).…”

Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy

“…Differential central and peripheral DNA methylation is reported lately in a variety of neurological and psychiatric disorders, with some studies showing a parallel pattern change in brain and blood derived samples43444546474849515253545556. For TLE, emerging data point to a potential role for aberrant epigenetic modulation in its etiology, pathogenesis or ictal pathophysiology3738394041425960, while less is known about the peripheral epigenetic change in this disorder.…”

“…Ion channel dysfunction represents a fundamental pathophysiological element underlying abnormal neuronal discharge in seizure disorders, with evidence supporting an involvement of genetic and epigenetic factors in epileptic channelopathies37396162. Mutations of the genes (SCN1A, SCN1B, SCN2A) coding some sodium channel subunits cause enhanced excitability of glutamatergic neurons and/or reduced excitability of GABAergic neurons in familial seizure disorders636465666768.…”

“…For instance, proteomic studies have shown remarkable and dynamic changes in protein expression involving multiple cellular systems in epileptic brain252627282930. Transcriptomic studies indicate that a few hundred genes are either up- or down-regulated in the ictogenic relative to unaffected brain regions31323334353637. Epigenetic changes are being recognized as a part of the molecular reconfiguration in TLE, with a wide array of genes involved in neuronal/synaptic transmission, cell survival/death and transcriptional regulation differentially methylated in the brains of patients3839404142.…”