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Anticonvulsant and antiepileptogenic effects of system x c - inactivation in chronic epilepsy models Vrije Universiteit Brussel

Karine Leclercq, Joeri Van Liefferinge, Giulia Albertini, Michel Neveux, Sylvia Dardenne, Georges Mairet-Coello, Catherine Vandenplas, Tania Deprez, Seon-Ah Chong, Patrik Foerch, et al.

OBJECTIVE: The cystine/glutamate antiporter system x c - could represent a new target for antiepileptogenic treatments due to its crucial roles in glutamate homeostasis and neuroinflammation. To demonstrate this, we compared epilepsy development and seizure susceptibility in xCT knockout mice (xCT-/- ) and in littermate controls (xCT+/+ ) in different chronic models of epilepsy.

METHODS: Mice were surgically implanted with electrodes ...

VESICULAR AND NON-VESICULAR ASTROCYTIC GLUTAMATE RELEASE IN TEMPORAL LOBE EPILEPSY Vrije Universiteit Brussel

Joeri Van Liefferinge
Epilepsy is one of the most common acquired chronic neurologic disorders, not only characterized by neuronal hyperexcitability and sudden, synchronized electrical discharges that can manifest as seizures, but also by an increased incidence of comorbid conditions such as anxiety, depression, cognitive dysfunction, and sudden unexpected death. About 70 million people worldwide suffer from epilepsy, with temporal lobe epilepsy (TLE) being is the ...

Caloric Restriction Protects against Lactacystin-Induced Degeneration of Dopamine Neurons Independent of the Ghrelin Receptor Vrije Universiteit Brussel

Jessica Coppens, Eduard Mihai Bentea, Jacqueline A Bayliss, Thomas Demuyser, Laura Walrave, Giulia Albertini, Joeri Van Liefferinge, Lauren Deneyer, Najat Aourz, Ann Van Eeckhaut, et al.
Parkinson's disease (PD) is a neurodegenerative disorder, characterized by a loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Caloric restriction (CR) has been shown to exert ghrelin-dependent neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-based animal model for PD. We here investigated whether CR is neuroprotective in the lactacystin (LAC) mouse model for PD, in which proteasome ...

Zonisamide attenuates lactacystin-induced parkinsonism in mice without affecting system xc(-) Vrije Universiteit Brussel KU Leuven

Eduard Mihai Bentea, Joeri Van Liefferinge, Lise Verbruggen, Katleen Martens, Lauren Deneyer, Thomas Demuyser, Giulia Albertini, Katrien Maes, Hideyo SATO, Ilse Smolders, et al.

Zonisamide (ZNS), an anticonvulsant drug exhibiting symptomatic effects in Parkinson's disease (PD), was recently reported to exert neuroprotection in rodent models. One of the proposed neuroprotective mechanisms involves increased protein expression of xCT, the specific subunit of the cystine/glutamate antiporter system xc(-), inducing glutathione (GSH) synthesis. Here, we investigated the outcome of ZNS treatment in a mouse model of PD ...

OXA-48 Producing Klebsiella pneumoniae in a Household Contact of a Previously Infected Patient: Person-to-Person Transmission or Coincidental Community Acquisition? Vrije Universiteit Brussel

Denis Pierard, Erlangga Yusuf, Anneleen Schallier, Yourri Glupczynki
We reported a woman with urinary-tract infection caused by OXA-48 producing Klebsiella pneumoniae. Using molecular techniques, we showed that she might acquire this bacterium from another family member who lived in the same house. The two isolates, although different by pulsed-field gel electrophoresis and multilocus sequence typing, carried blaOXA-48 in a similar IncL/M plasmid. This case report shows that community spreading of carbapenemase ...

Comparative analysis of antibodies to xCT (Slc7a11) Vrije Universiteit Brussel KU Leuven

Joeri Van Liefferinge, Eduard Mihai Bentea, Thomas Demuyser, Giulia Albertini, Virginie Follin-Arbelet, Silvia Holmseth, Ellen Merckx, Joeri Aerts, Ilse Smolders

The cystine/glutamate antiporter or system Xc- exchanges cystine for glutamate, thereby supporting intracellular glutathione synthesis and nonvesicular glutamate release. The role of system Xc- in neurological disorders can be dual and remains a matter of debate. One important reason for the contradictory findings that have been reported to date is the use of nonspecific anti-xCT (the specific subunit of system Xc-) antibodies. Often studies ...

Validation of the 6Hz refractory seizure mouse model for intracerebroventricularly administered compounds Vrije Universiteit Brussel

Laura Walrave, Katrien Maes, Jessica Coppens, Eduard Mihai Bentea, Ann Van Eeckhaut, Ann Massie, Joeri Van Liefferinge, Ilse Smolders

The six hertz (6Hz) refractory seizure model is considered an indispensable chain of the Anticonvulsant Screening Project. We here describe an adapted protocol using the intracerebroventricular (i.c.v.) delivery route, which will allow researchers to perform targetvalidation or proof-of-principle studies using promising compounds with unknown or limited blood-brain barrier permeability (e.g. neuropeptides and peptidomimetics) in this model. ...

Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin-Regulated Aminopeptidase Decreases Limbic Seizures. Vrije Universiteit Brussel

Dimitri De Bundel, Assia Fafouri, Zsolt Csaba, Ellen Loyens, Sophie Lebon, Vincent El Ghouzzi, Stéphane Peineau, Guilan Vodjdani, Foteini Kiagiadaki, Najat Aourz, et al.

UNLABELLED: Within the hippocampus, the major somatostatin (SRIF) receptor subtype, the sst2A receptor, is localized at postsynaptic sites of the principal neurons where it modulates neuronal activity. Following agonist exposure, this receptor rapidly internalizes and recycles slowly through the trans-Golgi network. In epilepsy, a high and chronic release of somatostatin occurs, which provokes, in both rat and human tissue, a decrease in the ...

Absence of system xc- in mice decreases anxiety and depressive-like behavior without affecting sensorimotor function or spatial vision Vrije Universiteit Brussel KU Leuven

Eduard Mihai Bentea, Thomas Demuyser, Joeri Van Liefferinge, Giulia Albertini, Lauren Deneyer, Julie Nys, Ellen Merckx, Yvette Michotte, Lutgarde Arckens

There is considerable preclinical and clinical evidence indicating that abnormal changes in glutamatergic signaling underlie the development of mood disorders. Astrocytic glutamate dysfunction, in particular, has been recently linked with the pathogenesis and treatment of mood disorders, including anxiety and depression. System xc- is a glial cystine/glutamate antiporter that is responsible for nonvesicular glutamate release in various ...

MPTP-induced parkinsonism in mice alters striatal and nigral xCT expression but is unaffected by the genetic loss of xCT Vrije Universiteit Brussel

Eduard Mihai Bentea, Michelle D Sconce, Madeline J Churchill, Joeri Van Liefferinge, Charles K Meshul, Ann Massie

Nigral cell loss in Parkinson's disease (PD) is associated with disturbed glutathione (GSH) and glutamate levels, leading to oxidative stress and excitotoxicity, respectively. System xc- is a plasma membrane antiporter that couples cystine import (amino acid that can be further used for the synthesis of GSH) with glutamate export to the extracellular environment, and can thus affect both oxidative stress and glutamate excitotoxicity. In the ...