GLT‐1 expression and Glu uptake in rat cerebral cortex are increased by phencyclidine

Fattorini, Giorgia; Melone, Marcello; Bragina, Luca; Candiracci, Chiara; Cozzi, Andrea; Giampietro, D. E. Pellegrini; Torres-Ramos, Mónica; Pérez-Samartı́n, Alberto; Matute, Carlos; Conti, Fiorenzo

doi:10.1002/glia.20700

Cited by 29 publications

(14 citation statements)

References 67 publications

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“…The discrepancies between the effective doses of sertindole in the 5-CSRTT and attentional set shifting might depend on differences in underlying neurochemical changes induced by acute and subchronic blockade of NMDA receptors. Acute and subchronic NMDA receptor antagonists had opposite effects on extracellular GLU in the mPFC (Fattorini et al 2008). However, differences in cognitive processes taxed by the tasks employed in different studies could not be disregarded since olanzapine and clozapine, which had no effects in attentional set shifting (Rodefer et al 2008) significantly attenuated the effect of subchronic PCP in a reversal learning paradigm (Abdul-Monim et al 2006).…”

Section: Discussionmentioning

confidence: 97%

Sertindole restores attentional performance and suppresses glutamate release induced by the NMDA receptor antagonist CPP

et al. 2010

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Section: Discussionmentioning

confidence: 97%

Sertindole restores attentional performance and suppresses glutamate release induced by the NMDA receptor antagonist CPP

et al. 2010

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“…This effect of TSG on GLT-1 protein expression in cultured astrocytes provided another reasonable explanation for the protective mechanism of TSG in brain ischemia, and this mechanism may be more important than that observed in previous studies [11], as drugs targeting astrocytic glutamate transporters to enhance their expressions and functions have been considered potential therapeutics for CNS disorders for a long time [21]. In previous studies, several compounds, including ceftriaxone [20], phencyclidine [22] and histone deacetylase inhibitors [23], have been reported to increase GLT-1 expression. Our work provides another potential candidate for the regulation of astrocytic glutamate transporters expressions.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of 2,3,4',5-Tetrahydroxystilbene 2-O-β-<smlcap>D</smlcap>-Glucoside-Induced Upregulation of Glutamate Transporter 1 Protein Expression in Mouse Primary Astrocytes

Chen¹,

Hu²,

Lu³

et al. 2017

Pharmacology

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Glutamate transporter-1 (GLT-1), a major glutamate transporter expressed in astrocytes, takes up excess glutamate from the micro-environment in order to prevent excitotoxicity. Drugs that increase GLT-1 expression may have therapeutic effects in disorders associated with neuronal excitotoxicity. 2,3,4',5-tetrahydroxystilbene 2-O-β-D-glucoside (TSG), a monomer of stilbene from polygonummultiflorum, exerts neuroprotection in a range of experimental models such as Alzheimer's disease and brain ischemia. In this study, we evaluated the effect of TSG on GLT-1 protein expression in mouse primary-cultured astrocytes. Results showed that TSG markedly increased the GLT-1 protein expression level in mouse primary-cultured astrocytes in a dose- and time-dependent manner, and this increase was mediated by the activation of protein kinase B (Akt) but not by the activation of extracellular signal-regulated protein kinase 1/2. Furthermore, inhibition of cAMP response element-binding protein, but not nuclear factor kappa B, abolished the TSG-mediated increase in GLT-1 protein expression in cultured astrocytes. Collectively, these findings may provide novel insights into the mechanism for TSG in neuroprotection, and would help search new agents targeting neurodegenerative disorders associated with impaired astrocytic glutamate transporters.

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“…Basically, substrate and nontransportable analogues (Munir et al 2000;Qu and Kanner 2008), signaling cascades (Li et al 2006;Sitcheran et al 2005), hormones (Autry et al 2006;Pawlak et al 2005;Dunlop et al 1999a) and a series of pharmacological agents (Chu et al 2007;Dunlop et al 1999b;Fattorini et al 2008) regulate GLT-1 expression and activity.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal glutamate transporter 1 (GLT-1) complex levels are paralleling memory training in the Multiple T-Maze in C57BL/6J mice

et al. 2011

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The glutamate transporter 1 (GLT-1) is essential for glutamate uptake in the brain and associated with various psychiatric and neurological disorders. Pharmacological inhibition of GLT-1 results in memory deficits, but no study linking native GLT-1 complexes was published so far. It was therefore the aim of the study to associate this highly hydrophobic, eight transmembrane spanning domains containing transporter to memory training in the Multiple T-maze (MTM). C57BL/6J mice were used for the spatial memory training experiments, and trained mice were compared to untrained (yoked) animals. Mouse hippocampi were dissected out 6 h after training on day 4, and a total enriched membrane fraction was prepared by ultracentrifugation. Membrane proteins were separated by blue native polyacrylamide gel electrophoresis (BN-PAGE) with subsequent Western blotting against GLT-1 on these native gels. Moreover, GLT-1 complexes were identified by mass spectrometry (nano-LC-ESI-MS/MS). Animals learned the MTM task and multiple GLT-1 complexes were detected at apparent molecular weights of 242, 480 and 720 kDa on BN-PAGE Western blotting. GLT-1 complex levels were significantly higher in the trained group as compared to yoked controls, and antibody specificity was verified by immunoblotting on multidimensional gels. Hippocampal GLT-1 was unambiguously identified by mass spectrometry with high sequence coverage, and glycosylation was observed. It is revealed that increased GLT-1 complex levels are paralleling and are linked to spatial memory training. We provide evidence that signal termination, represented by the excitatory amino acid transporter GLT-1 complexes, is involved in spatial memory mechanisms.

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GLT‐1 expression and Glu uptake in rat cerebral cortex are increased by phencyclidine

Cited by 29 publications

References 67 publications

Sertindole restores attentional performance and suppresses glutamate release induced by the NMDA receptor antagonist CPP

Sertindole restores attentional performance and suppresses glutamate release induced by the NMDA receptor antagonist CPP

Mechanism of 2,3,4',5-Tetrahydroxystilbene 2-O-β-<smlcap>D</smlcap>-Glucoside-Induced Upregulation of Glutamate Transporter 1 Protein Expression in Mouse Primary Astrocytes

Hippocampal glutamate transporter 1 (GLT-1) complex levels are paralleling memory training in the Multiple T-Maze in C57BL/6J mice

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