Neuronal Regulation of Glutamate Transporter Subtype Expression in Astrocytes

Swanson, Raymond A.; Liu, Jialing; Miller, Johann W.; Rothstein, Jeffrey D.; Farrell, Kevin; Stein, Becky A.; Longuemare, M. C.

doi:10.1523/jneurosci.17-03-00932.1997

Cited by 465 publications

(431 citation statements)

References 36 publications

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“…Thus, in immature forebrain, when mature synaptic patterns have not yet been established, glutamate transport by neurons may be dominant, whereas astroglial glutamate transport may predominate in mature forebrain at a time when synaptic innervation is f ully developed. This idea is consistent with the finding that GLT-1 is induced in undifferentiated astrocytes by the presence of neurons in vitro (Swanson et al, 1997). In addition, GLT-1 and GL AST, but not EAAC1, are mainly responsible for in vivo regulation of extracellular glutamate in adult brain (Rothstein et al, 1996), consistent with the finding that GLT-1 expression is transiently reduced in adult striatum after corticostriatal deafferentation (Ginsberg et al, 1995).…”

Section: Coordinated Expression Of Eaac1 and Glt-1 In Neonatal Brainsupporting

confidence: 90%

Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development

Furuta¹,

1997

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Extracellular glutamate concentrations are regulated by glial and neuronal transporter proteins. Four glutamate transporter subtypes have been identified in rat brain; GLAST and GLT-1 are primarily astrocytic, whereas EAAC1 and EAAT4 are neuronal. Using immunoblotting and immunohistochemistry with subtype-specific antipeptide antibodies, we examined the protein expression and regional and cellular localization of each glutamate transporter subtype in embryonic and postnatal rat CNS. Each transporter had a specific pattern of expression. GLAST immunoreactivity was low prenatally but became enriched in cerebellar Bergmann glia early postnatally and then was also present in forebrain later postnatally. The posttranslational modification of GLAST was unique among the subtypes; glycosylated GLAST increased with maturation, whereas nonglycosylated protein decreased in abundance postnatally. GLT-1 was present in fetal brain and spinal cord, with expression progressively increasing to adult levels throughout the neuraxis by postnatal day 26. Transient expression of GLT-1 immunoreactivity along axonal pathways was observed prenatally, in contrast to the exclusive localization of GLT-1 to astrocytes in the adult CNS. EAAC1, localized to neurons, was enriched in forebrain, diencephalon, and hindbrain during prenatal and postnatal development. EAAC1 expression was greater in newborn brain compared with adult brain. EAAT4 had a region-specific distribution; EAAT4 was mainly in cerebellum, localized to Purkinje cells, with much lower levels in forebrain. EAAT4 levels increased in cerebellum with age. We conclude that during CNS development the expression of glutamate transporter subtypes is differentially regulated, regionally segregated, and coordinated.

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Section: Coordinated Expression Of Eaac1 and Glt-1 In Neonatal Brainsupporting

confidence: 90%

Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development

Furuta¹,

1997

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“…3A2). A previous study has revealed that astrocytes co-cultured with neurons change from a polygonal to a process-bearing morphology that is more characteristic of astrocytes in situ (Swanson et al, 1997). The expression of astrocytic GLT-1 increases with such morphological changes of astrocytes (Gegelachvilli et al, 1997).…”

Section: Discussionmentioning

confidence: 92%

Reversed operation of glutamate transporter GLT‐1 is crucial to the development of preconditioning‐induced ischemic tolerance of neurons in neuron/astrocyte co‐cultures

Kikuchi

Kosugi

Tanaka

et al. 2004

Glia

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Sublethal ischemia leads to increased tolerance against subsequent prolonged cerebral ischemia in vivo. In the present study, we investigated the roles of the astrocytic glutamate (Glu) transporter GLT-1 in preconditioning (PC)-induced neuronal ischemic tolerance in cortical neuron/astrocyte co-cultures. Ischemia in vitro was simulated by subjecting cultures to both oxygen and glucose deprivation (OGD). A sublethal OGD (PC) significantly increased the survival rate of neurons when cultures were exposed to a lethal OGD 24 hr later. The extracellular concentration of Glu increased significantly during PC, and treatment with an inhibitor of NMDA receptors significantly reversed the PC-induced ischemic tolerance of neurons, suggesting that the increase in extracellular concentration of Glu during PC was critical to the development of PC-induced neuronal ischemic tolerance via the activation of NMDA receptors. Treatment with a GLT-1 blocker during PC significantly suppressed this increase in Glu, and antagonized the PC-induced neuronal ischemic tolerance. This study suggested that the reversed operation of GLT-1 was crucial to the development of neuronal ischemic tolerance.2

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“…(Bowman et al 2003;Conti et al 1994;Hosli and Hosli 1993;Imura et al 2006;Matthias et al 2003;Miller and Szigeti 1991;Nikcevich et al 1997;Porter and McCarthy 1995;Shao et al 1994;St-Pierre et al 2000;Swanson et al 1997;Venance et al 1998;Whitaker-Azmitia et al 1993;Zhou and Kimelberg 2001). For example, both in vitro and in vivo studies show that the expression of glutamate transporter isoforms GLT-1 and GLAST segregate to different hippocampal GFAP-positive astrocytes (Conti et al 1998;Perego et al 2000;van Landeghem et al 2006).…”

Section: Discussionmentioning

confidence: 99%

TGFβ1 and TNFα potentiate nitric oxide production in astrocyte cultures by recruiting distinct subpopulations of cells to express NOS-2

Hamby¹,

Gragnolati²,

Hewett³

et al. 2008

Neurochemistry International

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Nitric oxide (NO) synthase-2 (NOS-2), a key source of NO at sites of neuroinflammation, is induced in astrocyte cultures treated with lipopolysaccharide (LPS) plus interferon-γ (IFNγ). A recent study examining the regulation of astrocytic NOS-2 expression demonstrated that transforming growth factor-β1 (TGFβ1) potentiated LPS plus IFNγ-induced NOS-2 expression via expansion of the pool of astrocytes that express NOS-2. Results in the current report indicate that this population-based mechanism of increasing NOS-2 expression is not restricted to TGFβ1, since it also accounts for the potentiation of NO production in astrocyte cultures by tumor necrosis factor-α (TNFα). In contrast to TGFβ1, which required 24 hr preincubation for optimal potentiation of NO production, TNFα was maximally effective when added concurrently with LPS plus IFNγ. Nevertheless, under conditions that optimally potentiated NO production, both cytokines recruited similar numbers of astrocytes to express NOS-2 (% NOS-2-positive cells after LPS plus IFNγ alone or with TNFα or TGFβ1 was 9.5 ± 1.2, 25.3 ± 2.9, and 32.4 ± 3.0, respectively). Interestingly, stimulation of astrocytes in the presence of both TGFβ1 and TNFα additively increased the number of astrocytes that expressed NOS-2 protein (% NOS-2-positive cells was 61.0 ± 4.2) relative to each cytokine alone. Potentiation of NO production by either TNFα or TGFβ1 was not ablated by neutralizing antibodies to TGFβ1 or TNFα, respectively. Thus, the two cytokines act independently to recruit separate pools of astrocytes to express NOS-2. These results are consistent with the notion that astrocytes possess an innate heterogeneity with respect to responsiveness to these cytokines. KeywordsLPS; cytokines; heterogeneity; NO; iNOS; nitric oxide synthase Nitric oxide (NO) is an endogenously derived free radical gas that affects a spectrum of homeostatic and physiologic processes, including blood flow and coagulation, normal brain and heart function, and innate immunity (Belge et al. 2005;Ignarro et al. 1999;MacMicking et al. 1997;Yun et al. 1996). However, it can be harmful under certain pathophysiological conditions. Within the CNS, aberrant NO production has been linked to cerebrovascular dysfunction ( Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NO is derived from L-arginine by the catalytic action of three different NOS isoforms (Stuehr 1999). NOS-1 and -3 are constitutively expressed in neurons and endothelial cells, respectively, and thus were initially termed nNOS and eNOS. In contrast, NOS-2 is not constitutively expressed but can be induced ...

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Neuronal Regulation of Glutamate Transporter Subtype Expression in Astrocytes

Cited by 465 publications

References 36 publications

Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development

Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development

Reversed operation of glutamate transporter GLT‐1 is crucial to the development of preconditioning‐induced ischemic tolerance of neurons in neuron/astrocyte co‐cultures

TGFβ1 and TNFα potentiate nitric oxide production in astrocyte cultures by recruiting distinct subpopulations of cells to express NOS-2

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