Excitotoxicity in glial cells

Matute, Carlos; Alberdi, Elena; Ibarretxe, Gaskon; Sánchez‐Gómez, María Victoria

doi:10.1016/s0014-2999(02)01847-2

Cited by 126 publications

(77 citation statements)

References 62 publications

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“…In both instances, cell death is prevented by the removal of Ca 2+ from the culture medium and by AMPA/kainate receptor antagonists, but not by the blockade of other potential sources of Ca 2+ influx, which suggests that Ca 2+ entry through the receptor channel is sufficient to cell demise. These findings provided a direct link between ischemic damage to oligodendrocytes and excitotoxicity [67]. Notably, excitotoxic insults induce Ca 2+ overload into oligodendrocytes, oxidative stress, mitochondrial damage, and cell death by apoptosis or necrosis depending on the intensity of the insult [16].…”

Section: Hypoxia-ischemia Related Diseasesmentioning

confidence: 83%

Calcium and glial cell death

2005

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Calcium (Ca 2+ ) homeostasis is crucial for development and survival of virtually all types of cells including glia of the central nervous system (CNS). Astrocytes, oligodendrocytes and microglia, the major glial cell types in the CNS, are endowed with a rather sophisticated array of Ca 2+ -permeable receptors and channels, as well as store-operated channels and pumps, all of which determine Ca 2+ homeostasis. In addition, glial cells detect functional activity in neighbouring neurons and respond to it by means of Ca 2+ signals that can modulate synaptic interactions. Like in neurons, Ca 2+ overload resulting from dysregulation of channels and pumps can be deleterious to glia. In this review, we summarize recent advances in the understanding Ca 2+ homeostasis in glial cells, the consequences of its alteration in cell demise as well as in neurological and psychiatric disorders that experience glial cell loss.

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Section: Hypoxia-ischemia Related Diseasesmentioning

confidence: 83%

Calcium and glial cell death

2005

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“…White matter injury may arise following hypoxiaischemia at birth, but the largest patient cohort suffer injury during mid-gestation 1,2 . The motor, sensory and cognitive deficits that characterize the lesion are associated with injury to immature cells of the oligodendroglial lineage, which are susceptible to a form of non-NMDA-type glutamate receptor (GluR) -mediated excitotoxic injury [3][4][5][6][7][8] . In addition to non-NMDA receptors, these cells express NMDA GluRs selectively on their processes [9][10][11] , although the role of NMDA receptors in ischemic injury of myelinated white matter is controversial [12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

“…In addition to NMDA GluRs on their processes, developing oligodendroglia express non-NMDA receptors that can mediate toxic Ca 2+ -influx during ischemic conditions [3][4][5][6][7] . The current findings support the view that these receptors are expressed mainly on the somata 10 .…”

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confidence: 99%

Glutamate receptor‐mediated ischemic injury of premyelinated central axons

Alix

Fern

2009

Annals of Neurology

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ObjectiveIschemic injury of axons is a feature of periventricular leukomalacia, a pathological correlate of cerebral palsy. Recent evidence suggests that axons are damaged before they receive the first layer of compact myelin. Here we examine the cellular mechanisms underlying ischemic‐type injury of premyelinated central axons.MethodsTwo‐thirds of axons in the postnatal day 10 (P10) rat optic nerve are small premyelinated axons (<0.4μm in diameter), and one‐third have undergone radial expansion in preparation for glial contact and the onset of myelination. Compound action potential recording and quantitative electron microscopy were used to examine the effect of modeled ischemia (oxygen‐glucose deprivation) upon these two axon populations. Glutamate receptor (GluR) expression was investigated using polymerase chain reaction (PCR) and immunostaining approaches at the confocal light and ultrastructural levels.ResultsOxygen‐glucose deprivation produced action potential failure and focal breakdown of the axolemma of small premyelinated axons at sites of contact with oligodendrocyte processes, which were also disrupted. The resulting axon loss was Ca2+‐dependent, Na+‐ and Cl−‐independent, and required activation of N‐methyl‐D‐aspartic acid (NMDA) and non‐NMDA GluRs. NMDA receptor expression was localized to oligodendrocyte processes at sites of contact with premyelinated axons, in addition to expression within compact myelin. No periaxonal NMDA receptor expression was observed on oligodendrocyte processes ensheathing large premyelinated axons and no protective effect of GluR block was observed in these axons.InterpretationNMDA receptor‐mediated injury to oligodendrocyte processes navigating along small premyelinated axons precedes damage to the underlying axon, a phenomena that is lost following radial expansion and subsequent oligodendrocyte ensheathment. Ann Neurol 2009;66:682–693

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“…Glutamate, an excitatory neurotransmitter, is the most abundant neurotransmitter in the mammalian central nervous system, exerting several essential physiological functions (Matute et al, 2002). However, overstimulation of the glutamatergic system promotes excitotoxicity and is implicated in the pathology of PD (Hazell et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Effects of Systemic Administration of Iptakalim on Extracellular Neurotransmitter Levels in the Striatum of Unilateral 6-Hydroxydopamine-Lesioned Rats

Wang

Zhang

et al. 2005

Neuropsychopharmacol

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The function of ATP-sensitive potassium (KATP) channels in nigrostriatal pathway in Parkinson's disease (PD) was studied by employing a novel KATP channel opener iptakalim (Ipt). Apomorphine-induced rotation behavior test and microdialysis experiment were carried out in unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. Behavior test showed that systemic administration of Ipt failed to significantly alleviate apomorphine-induced rotation in unilateral 6-OHDA-lesioned PD model rats. However, using in vivo microdialysis in this PD model rats, it was found that Ipt could increase extracellular dopamine levels in the lesioned side of the striatum and decrease dopamine levels in the intact side of the striatum. Meanwhile, Ipt had no influence on glutamate levels in the intact side, but it did decrease glutamate levels in the lesioned side of the striatum of PD rats. Additionally, in primary cultured rat astrocytes, 6-OHDA decreased overall glutamate uptake activity, but this decrease was recovered and glutamate uptake activity was restored by the opening of KATP channels induced by Ipt and pinacidil. The classical KATP channel blocker glibenclamide completely abolished the effects of Ipt and pinacidil. The present study suggests that (i) the function of KATP channels in the lesioned and intact nigrostriatal pathway is different in unilateral 6-OHDA-lesioned PD model rats. (ii) KATP channels regulate extracellular neurotransmitter levels in the striatum of unilateral 6-OHDAlesioned rats and may play neuroprotective roles due to their effects on glutamate transporters. Neuropsychopharmacology (2006) 31, 933-940.

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Excitotoxicity in glial cells

Cited by 126 publications

References 62 publications

Calcium and glial cell death

Calcium and glial cell death

Glutamate receptor‐mediated ischemic injury of premyelinated central axons

Effects of Systemic Administration of Iptakalim on Extracellular Neurotransmitter Levels in the Striatum of Unilateral 6-Hydroxydopamine-Lesioned Rats

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