Characterization of striatal lesions produced by glutamate uptake alteration: Cell death, reactive gliosis, and changes in GLT1 and GADD45 mRNA expression

Liévens, Jean-Charles; Bernal, Fabián; Forni, Claude; Mahy, Nicole; Goff, Lydia Kerkerian‐Le

doi:10.1002/(sici)1098-1136(20000201)29:3<222::aid-glia4>3.0.co;2-0

Cited by 72 publications

(56 citation statements)

References 57 publications

(77 reference statements)

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“…GLAST and GLT-1 are expressed primarily in glial cells, whereas EAAC1 is the predominant neuronal GT (Robinson and Dowd, 1997;Danbolt, 2001). Both neuronal and glial GTs actively participate in a number of fundamental physiological functions, including synaptic plasticity, by regulating extracellular glutamate concentration (Mennerick et al, 1999;Lievens et al, 2000;Vorwerk et al, 2000;Trotti et al, 2001). Importantly, GTs regulate the duration and intensity of glutamate receptor activation during signal transduction.…”

Section: Introductionmentioning

confidence: 75%

“…Regulation of regional glutamate uptake has been linked critically to the prevention of glutamate neurotoxicity as well as the pathogenesis of neurological disorders, including brain ischemia, epilepsy, amyotrophic lateral sclerosis, spinal cord injury, and Alzheimer's disease (Mennerick et al, 1999;Lievens et al, 2000;Vorwerk et al, 2000;Bigini et al, 2001;Trotti et al, 2001;VeraPortocarrero et al, 2002). The present findings suggest a new strategy for treating neuropathic pain by reducing regional glutamate availability and preventing glutamate overexcitation via an enhanced GT system.…”

Section: Contributions To the Central Mechanisms Of Neuropathic Painmentioning

confidence: 98%

“…Although GTs also regulate aspartate uptake, only glutamate will be mentioned in the following to simplify the discussion. Several lines of evidence support a critical role of regulating GT expression and uptake activity in maintaining in vivo glutamate homeostasis as indicated in in vitro studies (Semba and Wakuta, 1998;Azbill et al, 2000;Jabaudon et al, 2000;Lievens et al, 2000;Matthews et al, 2000;Mu et al, 2000). First, in a previous study downregulation of spinal GTs induced by chronic morphine administration resulted in the exacerbated response to exogenous glutamate (Mao et al, 2002b).…”

Section: Overall Consideration On Data Interpretationmentioning

confidence: 99%

“…Importantly, GTs regulate the duration and intensity of glutamate receptor activation during signal transduction. As such, GTs play a critical role in preventing overstimulation of glutamate receptors, a process that could trigger both neuroplastic changes and excitotoxic cascades under a variety of pathological conditions, including spinal cord and peripheral nerve injury (Mennerick et al, 1999;Lievens et al, 2000;Vorwerk et al, 2000;Trotti et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Altered Expression and Uptake Activity of Spinal Glutamate Transporters after Nerve Injury Contribute to the Pathogenesis of Neuropathic Pain in Rats

2003

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The central glutamatergic system has been implicated in the pathogenesis of neuropathic pain, and a highly active central glutamate transporter (GT) system regulates the uptake of endogenous glutamate. Here we demonstrate that both the expression and uptake activity of spinal GTs changed after chronic constriction nerve injury (CCI) and contributed to neuropathic pain behaviors in rats. CCI induced an initial GT upregulation up to at least postoperative day 5 primarily within the ipsilateral spinal cord dorsal horn, which was followed by a GT downregulation when examined on postoperative days 7 and 14 by Western blot and immunohistochemistry. Intrathecal administration of the tyrosine kinase receptor inhibitor K252a and the mitogen-activated protein kinase inhibitor PD98059 for postoperative days 1-4 reduced and nearly abolished the initial GT upregulation in CCI rats, respectively. Prevention of the CCI-induced GT upregulation by PD98059 resulted in exacerbated thermal hyperalgesia and mechanical allodynia reversible by the noncompetitive NMDA receptor antagonist MK-801, indicating that the initial GT upregulation hampered the development of neuropathic pain behaviors. Moreover, CCI significantly reduced glutamate uptake activity of spinal GTs when examined on postoperative day 5, which was prevented by riluzole (a positive GT activity regulator) given intrathecally twice a day for postoperative days 1-4. Consistently, riluzole attenuated and gradually reversed neuropathic pain behaviors when the 4 d riluzole treatment was given for postoperative days 1-4 and 5-8, respectively. These results indicate that changes in the expression and glutamate uptake activity of spinal GTs may play a critical role in both the induction and maintenance of neuropathic pain after nerve injury via the regulation of regional glutamate homeostasis, a new mechanism relevant to the pathogenesis of neuropathic pain.

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Section: Introductionmentioning

confidence: 75%

Section: Contributions To the Central Mechanisms Of Neuropathic Painmentioning

confidence: 98%

Section: Overall Consideration On Data Interpretationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Altered Expression and Uptake Activity of Spinal Glutamate Transporters after Nerve Injury Contribute to the Pathogenesis of Neuropathic Pain in Rats

2003

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“…The complexity of the mechanisms involved in glutamatergic neurotransmission makes it already apparent that a number of 10/48 abnormalities, pre-synaptic, post-synaptic or glial, alone or in combination can be excitotoxic. For example, a loss of selectivity of ionotropic receptors [49], or deficiencies in glial re-uptake of glutamate [55] are observed in lateral amyotrophic sclerosis. In drug abuse, synaptic glutamate dysfunctions contribute to explain phenomena such as the effectiveness of either a mGluR1, mGluR5 or NMDA antagonist to inhibit the up regulation of endoplasmic reticulum stress protein due to acute and chronic cocaine administration [3].…”

Section: Excitotoxicity and Neurodegenerationmentioning

confidence: 99%

Substance-Related Disorders and Somatic Symptoms: How Should Clinicians Understand the Associations?

Yoshimasu

2012

CDAR

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Neuronal glutamate transporter EAAT4 is expressed in astrocytes

Walters

Xia

et al. 2003

Glia

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High-affinity excitatory amino acid transporters (EAATs) are essential to terminate glutamatergic neurotransmission and to prevent excitotoxicity. To date, five distinct EAATs have been cloned from animal and human tissues: GLAST (EAAT1), GLT-1 (EAAT2), EAAC1 (EAAT3), EAAT4, and EAAT5. EAAT1 and EAAT2 are commonly known as glial glutamate transporters, whereas EAAT3, EAAT4, and EAAT5 are neuronal. EAAT4 is largely expressed in cerebellar Purkinje cells. In this study, using immunohistochemistry and Western blotting, we found that EAAT4-like immunoreactivity (ir) is enriched in the spinal cord and forebrain. Double-labeled fluorescent immunostaining and confocal image analysis indicated that EAAT4-like ir colocalizes with an astrocytic marker, glial fibrillary acidic protein (GFAP). The astrocytic localization of EAAT4 was further confirmed in astrocyte cultures by double-labeled fluorescent immunocytochemistry and Western blotting. Reverse transcriptase-polymerase chain reaction analysis demonstrated mRNA expression of EAAT4 in astrocyte cultures. Sequencing confirmed the specificity of the amplified fragment. These results demonstrate that EAAT4 is expressed in astrocytes. This astrocytic localization of neuronal EAAT4 may reveal a new function of EAAT4 in the central nervous system.

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Characterization of striatal lesions produced by glutamate uptake alteration: Cell death, reactive gliosis, and changes in GLT1 and GADD45 mRNA expression

Cited by 72 publications

References 57 publications

Altered Expression and Uptake Activity of Spinal Glutamate Transporters after Nerve Injury Contribute to the Pathogenesis of Neuropathic Pain in Rats

Altered Expression and Uptake Activity of Spinal Glutamate Transporters after Nerve Injury Contribute to the Pathogenesis of Neuropathic Pain in Rats

Substance-Related Disorders and Somatic Symptoms: How Should Clinicians Understand the Associations?

Neuronal glutamate transporter EAAT4 is expressed in astrocytes

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