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. 
Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death
TLDR
It is demonstrated that chemical inhibition of the mitochondrial pyruvate carrier (MPC) protects primary cortical neurons from excitotoxic death and establishes the MPC as a therapeutic target to treat neurodegenerative diseases characterized by excitOToxicity.
Guanosine Neuroprotection of Presynaptic Mitochondrial Calcium Homeostasis in a Mouse Study with Amyloid-β Oligomers
TLDR
This endogenous purine presented a neuroprotective effect on presynaptic mitochondria and should be considered for further studies in AD models.
Magnetic Resonance Spectroscopy Studies in Bipolar Disorder Patients: Focus on the Potential Role of Oxidative Stress
TLDR
MRS studies exploring glutamate neurotransmission and specific neural energetic markers in BD are revised and the findings in relation to oxidative stress and mitochondrial dysfunction are debated.
AIF, reactive oxygen species, and neurodegeneration: A “complex” problem
  • B. Polster
  • Biology
    Neurochemistry International
  • 2013
Magnesium Sulfate Protects Against the Bioenergetic Consequences of Chronic Glutamate Receptor Stimulation
TLDR
Results indicate that MgSO4 protects against chronic moderate glutamate receptor stimulation and preserves cellular ATP following treatment with excitotoxic glutamate.
DHA Protects Against Zinc Mediated Alterations in Neuronal Cellular Bioenergetics
TLDR
Data suggest that zinc disrupts bioenergetics at a point distal to the respiratory chain, which is restored by DHA, which was specific for neuronal cells following chronic zinc exposure.
Zinc and docosahexaenoic acid metabolism in brain cells
This thesis examines the direct interaction of Docosahexaenoic acid (DHA, an omega-3 fatty acid) against zinc-induced mitochondrial dysfunction and involvement of bioenergetic regulation as a zinc
Mitochondrial bioenergetics and neuronal survival modelled in primary neuronal culture and isolated nerve terminals
TLDR
Recent advances have allowed synaptosomal bioenergetics to be studied on a microgram scale, and, in combination with approaches to correct for functional and transmitter heterogeneity, have allowed hypotheses concerning presynaptic mitochondrial dysfunction to be tested on a variety of genetic models of neurodegenerative disorders.
Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines
TLDR
It is demonstrated for the first time that lymphoblastoid cell lines derived from children with autistic disorder (AD) have an abnormal mitochondrial reserve capacity before and after exposure to reactive oxygen species (ROS), and a role for altered glutathione metabolism associated with this type of mitochondrial dysfunction is suggested.
...
1
2
3
4
5
...

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.
...
1
2
3
4
...