Abstract:
:In this study we investigated whether the link between mitochondrial dysfunction and deregulation of Ca(2+) homeostasis preceding excitotoxic cell death is mediated by cellular deenergization. Glycolytic and/or mitochondrial ATP synthesis was inhibited with 2-deoxy-D-glucose (2DG) and oligomycin, respectively. Changes in cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) and mitochondrial membrane potential were simultaneously measured in response to low (10 microM) glutamate concentrations, using the fluorescence dyes fura-2FF and rhodamine 123. 2DG, which blocks glycolysis and also inhibits mitochondrial respiration due to depletion of pyruvate, greatly increased and accelerated glutamate-induced elevation of [Ca(2+)](c) and mitochondrial depolarization. The 2DG-induced hypersensitivity to glutamate was observed even after 150-min washout of 2DG with glucose-containing medium, suggesting a permanent deterioration of mitochondrial function. Prior blockade of only glycolytic (2DG with pyruvate) or only mitochondrial (oligomycin) ATP synthesis did not affect neuronal sensitivity to glutamate. Collectively, these studies show that to maintain the sensitivity of neurons to glutamate at control levels at least one of the cellular sources of ATP production must be intact. Either glycolysis or oxidative phosphorylation can effectively support Ca(2+) homeostasis in cultured forebrain neurons.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Vergun O,Han YY,Reynolds IJdoi
10.1016/s0014-4886(03)00243-7keywords:
subject
Has Abstractpub_date
2003-10-01 00:00:00pages
682-94issue
2eissn
0014-4886issn
1090-2430pii
S0014488603002437journal_volume
183pub_type
杂志文章abstract::Infantile spasms are generalized convulsive seizures seen in the first year of life. They respond poorly to conventional anticonvulsants, but are often controlled by adrenocorticotropic hormone (ACTH) therapy. Other childhood seizures are also responsive to ACTH. The present study tested the effects of ACTH and relate...
journal_title:Experimental neurology
pub_type: 杂志文章
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abstract::Mutations of the PINK1 gene are a cause of autosomal recessive Parkinson's disease (PD). PINK1 encodes a mitochondrial kinase of unknown function which is widely expressed in both neuronal and non-neuronal cells. We have studied fibroblast cultures from four family members harbouring the homozygous p.Q456X mutation in...
journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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doi:10.1006/exnr.2000.7539
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journal_title:Experimental neurology
pub_type: 杂志文章
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abstract::This article reviews stem cell-based strategies for spinal cord injury repair, and practical issues concerning their translation to the clinic. Recent progress in the stem cell field includes clinically compliant culture conditions and directed differentiation of both embryonic stem cells and somatic stem cells. We pr...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1993.1021
更新日期:1993-02-01 00:00:00
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journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/0014-4886(92)90243-j
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90044-5
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journal_title:Experimental neurology
pub_type: 评论,杂志文章,评审
doi:10.1016/j.expneurol.2008.02.017
更新日期:2008-06-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
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doi:10.1016/0014-4886(85)90012-3
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(83)90308-4
更新日期:1983-06-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1999.7267
更新日期:2000-01-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90141-4
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1998.6948
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2012.01.023
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journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.09.023
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2005.05.001
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