Changes in expression of neuronal and glial glutamate transporters in rat hippocampus following kainate-induced seizure activity

Simantov, Rabi; Crispino, Marianna; Hoe, Warren; Broutman, Greg; Tocco, Georges; Rothstein, Jeffrey D.; Baudry, Michel

doi:10.1016/s0169-328x(98)00349-0

Cited by 90 publications

(66 citation statements)

References 38 publications

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“…By 24 h after SE, preliminary studies showed that the expression of GLAST and GLT-1 was not changed in the same brain regions as those where the expression of EAAC1 was increased (Voutsinos, unpublished data). These data are in agreement with previous studies reporting that, 16-24 h after the onset of SE, the expression of GLAST and GLT-1 was slightly reduced or unchanged, but never increased (Simantov et al, 1999;Doi et al, 2000). Thus, the neurodegeneration induced by prolonged lithiumpilocarpine seizures seems to depend on a lack of adaptation of all glutamate transporters, both neuronal and glial.…”

Section: Eaac1 Glutamate Transporters In Epilepsy B Voutsinos-porche supporting

confidence: 93%

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

Voutsinos-Porche

Koning

Clément

et al. 2006

J Cereb Blood Flow Metab

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Glutamate excitotoxicity has been involved in the pathophysiology of epilepsy. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. Using densitometric immunohistochemical analysis, we examined the temporal expression of the neuronal glutamate transporter (EAAC1) in the lithium-pilocarpine rat model of temporal lobe epilepsy. During the acute period of lithium-pilocarpine-induced status epilepticus, EAAC1 transporter expression increased in the pyramidal neurons of cornus ammonis (CA)1, CA2 and CA3 (fields of the hippocampus), in dentate gyrus (DG) granule cells and in olfactory tubercle (Tu). During the latent period, EAAC1 expression was strongly expressed in the DG granular and molecular layers, Tu, cerebral cortex and septum, and went back to control levels in CA1, CA2 and CA3 layers. The overexpression of EAAC1 occurred mainly in structures prone to develop FluoroJade-B-positive degenerating neurons. It is, however, not clear to what extent the overexpression of EAAC1 contributes to epileptogenesis and in which area it may represent a preventive or compensatory or response to injury.

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Section: Eaac1 Glutamate Transporters In Epilepsy B Voutsinos-porche supporting

confidence: 93%

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

Voutsinos-Porche

Koning

Clément

et al. 2006

J Cereb Blood Flow Metab

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“…In epilepsy, EAAC1 expression levels are known to be altered, which is considered a key factor in epileptogenesis (Ghijsen et al, 1999;Gorter et al, 2002;Simantov et al, 1999). The decreased expression levels of EAAC1 not only lead to the dysfunction in clearing synaptic glutamate but also result in the impairment of GABA synthesis (Maragakis and Rothstein, 2004;Sepkuty et al, 2002), and thus disrupts the balance between glutamate and GABA in the synaptic cleft.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, activation of protein kinase C (PKC) or platelet-derived growth factor receptor accelerates the delivery of EAAC1 to the cell surface and, at the same time, activation of PKC also inhibits the internalization of EAAC1 (Fournier et al, 2004). In the kainic acid (KA)-kindled model of epilepsy, the expression of EAAC1 is downregulated in the dentate gyrus, entorhinal cortex layer and hippocampus (Furuta et al, 2003;Ghijsen et al, 1999;Gorter et al, 2002;Simantov et al, 1999), especially with perinuclear deposits of EAAC1 (Furuta et al, 2003). Given the determinant role of trafficking in regulation of neurotransmitter transporters (Deken et al, 2000;Geerlings et al, 2001;Robinson, 2002), a greater understanding of the molecules that regulate EAAC1 trafficking is likely to shed light on this pivotal synaptic modulator.…”

Section: Introductionmentioning

confidence: 99%

Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport

Shen

Xia

et al. 2006

Journal of Cell Science

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The neuronal glutamate transporter, excitatory amino-acid carrier 1 (EAAC1), plays an important role in the modulation of neurotransmission and contributes to synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and to epileptogenesis. However, the mechanisms that regulate EAAC1 endocytic sorting and function remain largely unknown. Here, we first demonstrate that EAAC1 undergoes internalization through the clathrin-mediated pathway and further show that syntaxin 1A, a key molecule in synaptic exocytosis, potentiates EAAC1 internalization, thus leading to the functional inhibition of EAAC1. In the presence of the transmembrane domain of syntaxin 1A, its H3 coiled-coil domain of syntaxin 1A is necessary and sufficient for the inhibition of EAAC1. Furthermore, specific suppression of endogenous syntaxin 1A significantly blocked EAAC1 endocytic sorting and lysosomal degradation promoted by kainic acid, a drug for kindling the animal model of human temporal lobe epilepsy in rat, indicating a potential role of syntaxin 1A in epileptogenesis. These findings provide new evidence that syntaxin 1A serves as an intrinsic enhancer to EAAC1 endocytic sorting and further suggest that syntaxin 1A is conversant with both `ins' and `outs' of synaptic neurotransmission.

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“…Yet, in intact rats, a decrease in EAAT-3 immunoreactivity is observed in the stratum lacunosum moleculare 4 hours after the onset of seizures. Upon pyramidal cell loss (5 days after seizures), a total loss of EAAT-3 immunoreactivity is observed in CA1 and the stratum lacunosum moleculare (38). Our experiments show a rapid up-regulation of EAAT activity in hippocampal slices of rats killed 2 hours after the first forelimb clonus but not allowed to go into status epilepticus, whereas similarly treated rats allowed to survive for 48 hours (damage requires status epilepticus) have essentially the same EAAT activity as saline-injected rats.…”

Section: Discussionmentioning

confidence: 99%

Plasticity of Excitatory Amino Acid Transporters in Experimental Epilepsy

et al. 2000

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Summary:Purpose: To examine the relationship between seizures and excitatory amino acid transporter (EAAT) activity and whether up-regulation of EAAT activity alters epileptogenicity.Methods: In this study, we exposed rat hippocampal slices to different convulsants before measuring EAAT activity. Rats were exposed to the EAAT inhibitor pyrrolidine-2,4-dicarboxylic acid (PDC) before entorhinal cortex/hippocampal slices were obtained. These slices were exposed to low-Mg2+ buffer while electrophysiological recordings were obtained from the entorhinal cortex. mGluR I11 acting agents were used to study whether activation of mGluR I11 could regulate EAAT activity and if this regulation could overcome the effects on EAAT activity induced by the convulsants.Results: Veratridine, kainic acid (KA), and pilocarpine reduced EAAT activity in rat hippocampal slices. ~-2-Amino-4-phosphonobutyric acid (an mGluR I11 agonist) restored EAAT activity and reduced epileptiform activity to near control levels.The saturation curve for glutamate uptake in slices from KAseized rats killed 2 hours after the first forelimb clonus was displaced to the left, suggesting a compensatory change for the enhanced excitation. On the other hand, rats injected with the EAAT inhibitor PDC (by intracerebroventricular injection) had more severe KA-induced seizures and N-methyl-D-aspartate epileptiform activity than control rats. Furthermore, hippocampal slices from KA-or KA+PDC-treated rats exposed to low Mg2+ reduced their firing rate to nearly zero once they returned to normal solution, whereas their control counterparts continued to fire, although at a lower rate.Conclusions: These results suggest a significant contribution of EAATs in some experimental epilepsy models and point to their short-term regulation by mGluR 111 as a possible source of their plasticity.

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Changes in expression of neuronal and glial glutamate transporters in rat hippocampus following kainate-induced seizure activity

Cited by 90 publications

References 38 publications

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

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

Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport

Plasticity of Excitatory Amino Acid Transporters in Experimental Epilepsy

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