Spare respiratory capacity, oxidative stress and excitotoxicity.

@article{Nicholls2009SpareRC,
  title={Spare respiratory capacity, oxidative stress and excitotoxicity.},
  author={David G. Nicholls},
  journal={Biochemical Society transactions},
  year={2009},
  volume={37 Pt 6},
  pages={
          1385-8
        }
}
  • D. Nicholls
  • Published 1 December 2009
  • Biology
  • Biochemical Society transactions
Chronic exposure to glutamate (glutamate excitotoxicity) exacerbates neuronal damage in the aftermath of stroke and is implicated in a variety of neurodegenerative disorders. Mitochondria play a central role in the survival or death of the exposed neuron. Calcium, oxidative stress and ATP insufficiency play closely interlocked roles that may be investigated with primary neuronal cultures. 
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References

SHOWING 1-10 OF 39 REFERENCES
Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease.
  • D. Nicholls
  • Biology
    The international journal of biochemistry & cell biology
  • 2002
Glutamate-induced neuron death requires mitochondrial calcium uptake
TLDR
Results indicate that very high levels of cytoplasmic calcium are not necessarily toxic to forebrain neurons, and that potential-driven uptake of calcium into mitochondria is required to trigger NMDA-receptor-stimulated neuronal death.
NMDA-dependent superoxide production and neurotoxicity
TLDR
It is reported that O·- 2 is produced upon NMDA receptor stimulation in cultured cerebellar granule cells and the nitrone DMPO (5,5-dimethyl pyrroline 1-oxide), used as a spin trap, is more efficient than the nitric oxide synthase inhibitor, L-N G -nitroarginine, in reducing NMDA-induced neuronal death in these cultures.
In Situ Respiration and Bioenergetic Status of Mitochondria in Primary Cerebellar Granule Neuronal Cultures Exposed Continuously to Glutamate*
TLDR
It is concluded that excitotoxicity under these conditions is not because of an ATP deficit or uncoupling, and mitochondria maintain the same respiratory capacity as in control cells.
Glutamate and the pathophysiology of hypoxic–ischemic brain damage
TLDR
It is suggested that glutamate plays a key role in ischemic brain damage, and that drugs which decrease the accumulation of glutamate or block its postsynaptic effects may be a rational therapy for stroke.
Spare Respiratory Capacity Rather Than Oxidative Stress Regulates Glutamate Excitotoxicity after Partial Respiratory Inhibition of Mitochondrial Complex I with Rotenone
TLDR
It is concluded that the cell vulnerability in the rotenone model of partial complex I deficiency under these specific conditions is primarily determined by spare respiratory capacity rather than oxidative stress.
Mitochondria, Calcium Regulation, and Acute Glutamate Excitotoxicity in Cultured Cerebellar Granule Cells
TLDR
It is concluded that mitochondrial Ca 2+ accumulation is a necessary intermediate in glutamate excitotoxicity, whereas the decreased Ca2+ flux into cells with depolarized mitochondria may reflect a feedback inhibition of the NMDA receptor mediated by localized Ca2- accumulation in a microdomain accessible to the mitochondria.
Acute Glutathione Depletion Restricts Mitochondrial ATP Export in Cerebellar Granule Neurons*
TLDR
The initial bioenergetic consequence of neuronal GSH depletion in this model is an inhibition of ATP export, which precedes other forms of mitochondrial dysfunction, suggesting adequate glycolysis and a functional electron transport chain.
Excitotoxic Calcium Overload in a Subpopulation of Mitochondria Triggers Delayed Death in Hippocampal Neurons
TLDR
A mechanism in which delayed excitotoxic death involves apoptogen release from a subpopulation of calcium-overloaded mitochondria, whereas other, undamaged mitochondria maintain normal function is supported, supported by measured concentrations of total Ca in individual mitochondria.
Glutamate becomes neurotoxic via the N-methyl-d-aspartate receptor when intracellular energy levels are reduced
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