EAAC1 Glutamate Transporter Expression in the Rat Lithium-Pilocarpine Model of Temporal Lobe Epilepsy

Voutsinos-Porche, Brigitte; Koning, Estelle; Clément, Yann; Kaplan, Hervé; Ferrandon, Arielle; Motté, Jacques; Nehlig, Astrid

doi:10.1038/sj.jcbfm.9600295

Cited by 25 publications

(16 citation statements)

References 52 publications

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“…Interestingly, increased Golgi localization of EAAC1, and redistribution of the transporter between intracellular and surface membranes has been reported in a kainic acidinduced rodent epilepsy model (51). Furthermore, increased protein expression of EAAC1 has been observed in the pilocarpine model of epilepsy (52,53). In addition, other proteins such as ␤3 spectrin (GTRAP41) and PDZrhoGEF (GTRAP48) have been identified that regulate cytoplasmic and plasma membrane distribution of the neuronal glutamate transporter EAAT4 (54,55).…”

Section: Discussionmentioning

confidence: 99%

Reticulon RTN2B Regulates Trafficking and Function of Neuronal Glutamate Transporter EAAC1

Liu

Vidensky

Ruggiero

et al. 2008

Journal of Biological Chemistry

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Excitatory amino acid transporters (EAATs) are the primary regulators of extracellular glutamate concentrations in the central nervous system. Their dysfunction may contribute to several neurological diseases. To date, five distinct mammalian glutamate transporters have been cloned. In brain, EAAC1 (excitatory amino acid carrier 1) is the primary neuronal glutamate transporter, localized on the perisynaptic membranes that are near release sites. Despite its potential importance in synaptic actions, little is known concerning the regulation of EAAC1 trafficking from the endoplasmic reticulum (ER) to the cell surface. Previously, we identified an EAAC1-associated protein, GTRAP3-18, an ER protein that prevents ER exit of EAAC1 when induced. Here we show that RTN2B, a member of the reticulon protein family that mainly localizes in the ER and ER exit sites interacts with EAAC1 and GTRAP3-18. EAAC1 and GTRAP3-18 bind to different regions of RTN2B. Each protein can separately and independently form complexes with EAAC1. RTN2B enhances ER exit and the cell surface composition of EAAC1 in heterologous cells. Expression of short interfering RNA-mediated knockdown of RTN2B decreases the EAAC1 protein level in neurons. Overall, our results suggest that RTN2B functions as a positive regulator in the delivery of EAAC1 from the ER to the cell surface. These studies indicate that transporter exit from the ER controlled by the interaction with its ER binding partner represents a critical regulatory step in glutamate transporter trafficking to the cell surface.

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Section: Discussionmentioning

confidence: 99%

Reticulon RTN2B Regulates Trafficking and Function of Neuronal Glutamate Transporter EAAC1

Liu

Vidensky

Ruggiero

et al. 2008

Journal of Biological Chemistry

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“…Recurrent seizures started around 20-25 min after pilocarpine administration. These seizures which associated episodes of head and bilateral forelimb myoclonus with rearing and falling progressed to SE at approximately 35-40 min after pilocarpine injection, as described previously [22][23][24]. Drugs were given i.p.…”

Section: Induction Of Seizuresmentioning

confidence: 99%

Involvement of Nitric Oxide in Spatial Memory Deficits in Status Epilepticus Rats

2007

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Status epilepticus (SE) is associated with a significant risk of cognitive impairment, and the increase of nitric oxide (NO) releasing has been reported during SE. We investigated the effects of neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI) and inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AG), on spatial performance of rats in the Morris water maze. Treatment with 7-NI, but not with AG, improved the performance of rats after SE not only in acquisition of the task but also in probe test. Furthermore, the level of SE-induced malondialdehyde (MDA), end product of lipid peroxidation, was significantly decreased only in animals receiving 7-NI injection. Taken together, the results of the present study provided evidence that the NO pathway contributed to oxidative stress after SE, and nNOS/NO pathway may underlie one of the potential mechanisms contributing to SE-induced spatial memory deficits.

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“…Up regulation of glutamate transporter proteins is thought to be a compensatory response following the acute phase of status epilepticus with hypoxia, having an effect as observed with kainic acid [7,54,58,61]. Glutamate transporters reverse when ion gradients are affected in anoxia or ischemia [9,39].…”

Section: Discussionmentioning

confidence: 97%

“…A reduction of uptake by the glutamate transporters could explain excessive excitability in epileptic foci [45,49,53]. Meanwhile, up regulation of glutamate transporter proteins is thought to be a compensatory mechanism in the acute phase following status epilepticus [7,58,61]. Diminished GABA transporter levels could decreased GABA removal and thus increase inhibition [2,25,30,34,41].…”

Section: Introductionmentioning

confidence: 97%

Role of Glutamate and GABA Transporters in Development of Pentylenetetrazol-Kindling

et al. 2009

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Kindling is a form of epileptogenesis that can be induced with pentylenetetrazol (PTZ). We undertook this study to evaluate the contribution of glutamate and GABA transporters to the process of PTZ kindling. Rats were injected i.p. three times per week with PTZ (40 mg/kg) until they were fully kindled. In rats who achieved full kindling, measurement of hippocampal glutamate and GABA transporters within 24 h by western blot showed that GLAST, GLT-1, and EAAC1 were elevated significantly. However, fully kindled rats at 30 days after their last seizure had no change in either glutamate or GABA transporters proteins. These sequential observations suggest that glutamate transporters may contribute to the occurrence of seizures, but were not associated with maintenance of epileptogenesis. During this experiment, we collected data from animals that had kindled easily and animals who were resistant to kindling. Easily-kindled rats reached full kindling with less than five injections of PTZ. Kindling resistant animals failed to achieve full kindling even after administration of 12 consecutive injections of PTZ. Levels of EAAC1 and GAT-1 in easily-kindled rats were decreased by 30% when compared to kindling resistant animals at 30 days after the last PTZ injection. Since decreased EAAC1 and GAT-1 would diminish GABA function, less quantity of these proteins would appear to be associated with the convulsive threshold at the beginning of kindling development. We wonder if glutamate and GABA transporters might be operant in a convulsion threshold set factor or as a pace factor for kindling.

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EAAC1 Glutamate Transporter Expression in the Rat Lithium-Pilocarpine Model of Temporal Lobe Epilepsy

Cited by 25 publications

References 52 publications

Reticulon RTN2B Regulates Trafficking and Function of Neuronal Glutamate Transporter EAAC1

Reticulon RTN2B Regulates Trafficking and Function of Neuronal Glutamate Transporter EAAC1

Involvement of Nitric Oxide in Spatial Memory Deficits in Status Epilepticus Rats

Role of Glutamate and GABA Transporters in Development of Pentylenetetrazol-Kindling

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