Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Liefferinge, Joeri Van; Massie, Ann; Portelli, Jeanelle; Giovanni, Giuseppe Di; Smolders, Ilse Julia

doi:10.3389/fncel.2013.00139

Cited by 53 publications

(27 citation statements)

References 256 publications

(377 reference statements)

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“…Genetic mutations enhancing structural and functional alterations of key proteins including pre-synaptic complexes (Toader et al, 2013) and potassium channels (D'Adamo et al, 2013) are also related to the occurrence of epileptic disorders. Consistently with these findings obtained in genetic animal models of epilepsy, studies conducted in animal models of acquired epilepsy addressed the critical role of vesicular neurotransmitters transporters (VNTs) (Van Liefferinge et al, 2013) and non-neuronal potassium channel (Kir4.1) (Nagao et al, 2013) expression during epileptogenesis.…”

supporting

confidence: 61%

Neuronal mechanisms of epileptogenesis

2015

Frontiers Research Topics

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supporting

confidence: 61%

Neuronal mechanisms of epileptogenesis

2015

Frontiers Research Topics

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“…Collectively, additional evidence has been found to support a possible involvement of VGLUTs in TLE, but still more and better experimental tools, such as specific inhibitors, are required (for review see [34]). Finally, it should be mentioned that antiepileptic drug treatment might affect VGLUT expression.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have investigated, VGLUT1 and VGLUT2 mRNA and/or protein levels in distinct animal models of epilepsy (for review see [34]). In addition, the involvement of VGLUT2 and VGLUT3 in, respectively, generalized and absence seizures has been proposed [23,25].…”

Section: Introductionmentioning

confidence: 99%

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

Liefferinge

Jensen

Albertini

et al. 2015

Neuroscience Letters

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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...

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“…Most, if not all of the approved antiepileptic drugs (AEDs) are not truly “antiepileptic” but merely “anti-seizures” (Van Liefferinge et al, 2013). Indeed, the AEDs do not stop epileptogenesis, the process of converting a normal brain to a brain with epilepsy, but at the most they reach complete seizure control.…”

Section: Introductionmentioning

confidence: 99%

Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

et al. 2016

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A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders.

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Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Cited by 53 publications

References 256 publications

Neuronal mechanisms of epileptogenesis

Neuronal mechanisms of epileptogenesis

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

Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

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