Regulation of astrocyte glutamine synthetase in epilepsy

Eid, Tore; Tu, Nathan; Lee, Tih‐Shih W.; Lai, James C. K.

doi:10.1016/j.neuint.2013.06.008

Cited by 96 publications

(80 citation statements)

References 174 publications

(252 reference statements)

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“…The evidence that GS levels are significantly decreased in the human hippocampus and amygdala in temporal lobe epilepsy further corroborated critical role of this enzyme in epileptogenesis (Eid et al ., 2013). Such assumption was aslo supported by the observation that reduced GS expression induced by gene mutations resulted in severe seizures (Haberle et al ., 2011).…”

Section: Epilepsysupporting

confidence: 61%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain.

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Section: Epilepsysupporting

confidence: 61%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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“…These alterations are responsible for the relatively high intracellular chloride concentration that depolarizes the membrane upon stimulation of ionotropic GABA receptors, resulting in reduced inhibition and neuronal hyperexcitability (see above). Neuronal cell death initiated by excitotoxicity is thought to be exacerbated by the loss of astrocyte-neuron cell-cell contact following the deterioration in extracellular matrix proteins (Eid et al, 2013b). These events trigger a number of changes in astrocytic gene expression that have been found to increase protein nitration, oxidative stress and also β-amyloid deposits that ultimately lead to reduction in astrocytic GS (Eid et al, 2008b).…”

Section: How Excess Glutamate Can Impair K+ Homeostasismentioning

confidence: 99%

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

et al. 2014

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Epilepsy is a heterogeneous family of neurological disorders that manifest as seizures, i.e. the hypersynchronous activity of large population of neurons. About 30% of epileptic patients do not respond to currently available antiepileptic drugs. Decades of intense research have elucidated the involvement of a number of possible signaling pathways, however, at present we do not have a fundamental understanding of epileptogenesis. In this paper, we review the literature on epilepsy under a wide-angle perspective, a mandatory choice that responds to the recurrent and unanswered question about what is epiphenomenal and what is causal to the disease. While focusing on the involvement of K+ and glutamate/GABA in determining neuronal hyperexcitability, emphasis is given to astrocytic contribution to epileptogenesis, and especially to loss-of-function of astrocytic glutamine synthetase following reactive astrogliosis, a hallmark of epileptic syndromes. We finally introduce the potential involvement of abnormal glycogen synthesis induced by excess glutamate in increasing susceptibility to seizures.

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“…The ensuing excitotoxicity may be a causative factor in multitude of neurodegenerative diseases (Dawson et al, 1995;Dong et al, 2009). Astrocytes play a crucial role in regulating and maintaining the extracellular chemical milieu of the central nervous system under physiological conditions (Eid et al, 2013). In, the conversion of glutamate to glutamine by glutamine synthetase, that takes place within the astrocytes, represents a key mechanism in the regulation of excitatory neurotransmission under normal conditions as well as in injured brain (Szatkowski and Attwell, 1994).…”

Section: Introductionmentioning

confidence: 99%

“…Thus GS is involved in modulation of the turnover of glutamate through the glutamate-glutamine cycle (Van der berg and Garfinkel, 1971). The known stoichiometry of glutamate transport across the astrocyte plasma membrane also suggests that rapid metabolism of intracellular glutamate via glutamine synthetase (GS) is a prerequisite for efficient glutamate clearance from the extracellular space (Eid et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Restoration Of Glutamine Synthetase Activity, Nitric Oxide Levels And Amelioration Of Oxidative Stress By Propolis In Kainic Acid Mediated Excitotoxicity

Swamy

Norlina

Azman

et al. 2014

Afr. J. Trad. Compl. Alt. Med.

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Background: Propolis has been proposed to be protective on neurodegenerative disorders. To understand the neuroprotective effects of honeybee propolis, glutamine synthetase (GS) activity, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAS) were studied in different brain regions-cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats supplemented with propolis and subjected to kainic acid (KA) mediated excitotoxicity. Materials and Methods: Male Sprague-Dawley rats were divided into four groups; Control group and KA group received vehicle and saline. Propolis group and propolis + KA group were orally administered with propolis (150mg/kg body weight), five times every 12 hours. KA group and propolis + KA group were injected subcutaneously with kainic acid (15mg/kg body weight) and were sacrificed after 2 hrs and CC, CB and BS were separated homogenized and used for estimation of GS activity, NO, TBARS, and TAS concentrations by colorimetric methods. Results were analyzed by oneway ANOVA, reported as mean + SD from 6 animals, and p<0.05 considered statistically significant. Results: NO was increased (p< 0.001) and GS activity was decreased (p< 0.001) in KA treated group compared to control group as well as propolis + KA treated group. TBARS was decreased and TAS was increased (p< 0.001) in propolis + KA treated group compared KA treated group. Conclusion:This study clearly demonstrated the restoration of GS activity, NO levels and decreased oxidative stress by propolis in kainic acid mediated excitotoxicity. Hence the propolis can be a possible potential candidate (protective agent) against excitotoxicity and neurodegenerative disorders.

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Regulation of astrocyte glutamine synthetase in epilepsy

Cited by 96 publications

References 174 publications

Translational potential of astrocytes in brain disorders

Translational potential of astrocytes in brain disorders

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

Restoration Of Glutamine Synthetase Activity, Nitric Oxide Levels And Amelioration Of Oxidative Stress By Propolis In Kainic Acid Mediated Excitotoxicity

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