Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes

Gegelashvili, Georgi; Civenni, Gianluca; Racagni, Giorgio; Danbolt, Niels Christian; Schousboe, Inger; Schousboe, Arne

doi:10.1097/00001756-199612200-00052

Cited by 162 publications

(121 citation statements)

References 10 publications

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“…Postnatal cortical astrocytes tend to grow as mixed glial cell populations, mainly astrocytes but with a higher proportion of microglia. Such cultures take longer to become confluent and whilst they too express high levels of GLAST; GLT-1 levels decrease over time, with the functional burden of glutamate transport assumed by GLAST [48,50]. Indeed, research has shown that GLAST mediates the majority of L-glutamate uptake in postnatal cortical astrocyte cultures (28)(29)(30)(31)(32)(33)(34)(35), correlating with increased cell surface expression of GLAST [22].…”

Section: Discussionmentioning

confidence: 99%

Astrocytes Grown in Alvetex® Three Dimensional Scaffolds Retain a Non-reactive Phenotype

2016

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Protocols which permit the extraction of primary astrocytes from either embryonic or postnatal mice are well established however astrocytes in culture are different to those in the mature CNS. Three dimensional (3D) cultures, using a variety of scaffolds may enable better phenotypic properties to be developed in culture. We present data from embryonic (E15) and postnatal (P4) murine primary cortical astrocytes grown on coated coverslips or a 3D polystyrene scaffold, Alvetex. Growth of both embryonic and postnatal primary astrocytes in the 3D scaffold changed astrocyte morphology to a mature, protoplasmic phenotype. Embryonic-derived astrocytes in 3D expressed markers of mature astrocytes, namely the glutamate transporter GLT-1 with low levels of the chondroitin sulphate proteoglycans, NG2 and SMC3. Embroynic astrocytes derived in 3D show lower levels of markers of reactive astrocytes, namely GFAP and mRNA levels of LCN2, PTX3, Serpina3n and Cx43. Postnatal-derived astrocytes show few protein changes between 2D and 3D conditions. Our data shows that Alvetex is a suitable scaffold for growth of astrocytes, and with appropriate choice of cells allows the maintenance of astrocytes with the properties of mature cells and a non-reactive phenotype.

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Section: Discussionmentioning

confidence: 99%

Astrocytes Grown in Alvetex® Three Dimensional Scaffolds Retain a Non-reactive Phenotype

2016

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“…Glutamate is known to trigger a rapid increase in surface expression of GLAST and EAAT4 [41]. Other factors that may play a role include activation of glutamate receptors on glia [43], modulation of GLAST expression by growth factors such as insulin growth factor-1, oxidative stress [44], arachidonic acid [45], or protein kinase C [46]. Other factors such as plasma that leak from the break down of the blood-retinal barrier can also alter ion channel conductance within Müller cells [29].…”

Section: Discussionmentioning

confidence: 99%

Glutamate uptake in retinal glial cells during diabetes

et al. 2005

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Aims: Glutamate recycling is a major function of retinal Müller cells. The aim of this study was to evaluate the expression and function of glutamate transporters during diabetes. Methods: Sprague-Dawley rats were rendered diabetic by a single dose of streptozotocin (50 mg/kg). Following 12 weeks of diabetes, immunolocalisation and mRNA expression of the two glial cell transporters, GLAST and EAAT4 were evaluated using indirect immunofluorescence and real-time PCR. The function of glutamate transport was investigated at 1, 4 and 12 weeks following induction of diabetes by measuring the level of uptake of the non-metabolisable glutamate analogue, D-aspartate, into Müller cells. Results: There was no difference in the localisation of either GLAST or EAAT4 during diabetes. Although there was a small apparent increase in expression of both GLAST and EAAT4 in diabetic retinae compared with controls this was not statistically significant. At 1, 4 and 12 weeks following diabetes, D-aspartate immunoreactivity was significantly increased in Müller cells of diabetic rats compared to controls (p<0.001). The EC 50 was found to increase by 0.304 log units in diabetic Müller cells compared with controls, suggesting that glutamate uptake is twice as efficient. Conclusions: These data suggest that there are alterations in glutamate transport during diabetes. However, these changes are unlikely to play a significant role in glutamate-induced neuronal excitoxicity during diabetes. These results suggest that although Müller cells undergo gliosis at an early stage of diabetes, one of the most important functions for maintaining normal retinal function is preserved within the retina.

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“…The decreased removal of Glu from the synapse would then lead to excitotoxicity, causing blebbing and dieback of neurites. These damaged neurons may then signal to surviving astrocytes, perhaps via release of Glu, to induce an adaptive increase in the V max of Glu uptake, a process resembling the feedback regulatory loop occuring during excitatory transmission to maintain Glu homeostasis (Duan et al, 1999;Gegelashvili et al, 1996). With continued oxidative stress and excitotoxicity, and the interdependence between these two mechanisms (Trotti et al, 1998), these homeostatic responses cannot be maintained indefinitely and neurotoxicity will occur.…”

Section: Zagami Et Almentioning

confidence: 99%

Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis

Zagami

Beart

Wallis

et al. 2008

Glia

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In amyotrophic lateral sclerosis (ALS) non-neuronal cells play key roles in disease etiology and loss of motoneurons via noncell-autonomous mechanisms. Reactive astrogliosis and dysfunctional transporters for L-glutamate [excitatory amino acid transporters, (EAATs)] are hallmarks of ALS pathology. Here, we describe mechanistic insights into ALS pathology involving EAAT-associated homeostasis in response to a destructive milieu, in which oxidative stress and excitotoxicity induce respectively astrogliosis and motoneuron injury. Using an in vitro neuronal-glial culture of embryonic mouse spinal cord, we demonstrate that EAAT activity was maintained initially, despite a loss of cellular viability induced by exposure to oxidative [3-morpholinosydnonimine chloride (SIN-1)] and excitotoxic [(S)-5-fluorowillardiine (FW)] conditions. This homeostatic response of EAAT function involved no change in the cell surface expression of EAAT1/2 at 0.5-4 h, but rather alterations in kinetic properties. Over this time-frame, EAAT1/2 both became more widespread across astrocytic arbors in concert with increased expression of glial fibrillary acidic protein (GFAP), although at 8-24 h there was gliotoxicity, especially with SIN-1 rather than FW. An opposite picture was found for motoneurons where FW, not SIN-1, produced early and extensive neuritic shrinkage and blebbing ( 0.5 h) with somata loss from 2 h. We postulate that EAATs play an early homeostatic and protective role in the pathologic milieu. Moreover, the differential profiles of injury produced by oxidative and excitotoxic insults identify two distinct phases of injury which parallel important aspects of the pathology of ALS. V V C

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Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes

Cited by 162 publications

References 10 publications

Astrocytes Grown in Alvetex® Three Dimensional Scaffolds Retain a Non-reactive Phenotype

Astrocytes Grown in Alvetex® Three Dimensional Scaffolds Retain a Non-reactive Phenotype

Glutamate uptake in retinal glial cells during diabetes

Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis

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