Mild Acidosis Protects Neurons during Oxygen-Glucose Deprivation by Reducing Loss of Mitochondrial Respiration

Brain ischemia is often accompanied by brain acidosis and this acidosis can affect ischemic neuronal injury. Ischemic neuronal injury is initiated by a decrease in ATP production which mainly relies on mitochondrial oxidative phosphorylation. Ischemia often causes mitochondrial dysfunction, and acid...

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Bibliographic Details
Published in:ACS chemical neuroscience 2019-05, Vol.10 (5), p.2489-2497
Main Authors: Zhu, Ming-Yue, Zhang, Dong-Liang, Zhou, Chen, Chai, Zhen
Format: Article
Language:English
Subjects:
Acidosis - physiopathology
Adenosine Triphosphate - metabolism
Adenosine Triphosphate - physiology
Animals
Blood Glucose - metabolism
Brain Ischemia - physiopathology
Cell Respiration - physiology
Disease Models, Animal
Female
Hydrogen-Ion Concentration
Hypoxia - physiopathology
Male
Mitochondria - physiology
Neurons - physiology
Neuroprotection - physiology
Oxygen - metabolism
Oxygen Consumption - physiology
Rats, Sprague-Dawley
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Summary:Brain ischemia is often accompanied by brain acidosis and this acidosis can affect ischemic neuronal injury. Ischemic neuronal injury is initiated by a decrease in ATP production which mainly relies on mitochondrial oxidative phosphorylation. Ischemia often causes mitochondrial dysfunction, and acidosis has been found to affect mitochondrial function, suggesting that acidosis accompanying ischemia may influence neurons by targeting mitochondrial metabolism. However, the effects of acidosis on mitochondrial energy metabolism during ischemia lacks thorough investigation. Here, we found that mild acidosis significantly reduced neuronal death possibly by slowing the process of ATP deprivation during oxygen-glucose deprivation (OGD), an in vitro ischemic model. The maintaining of neuronal ATP depended on protecting mitochondrial ATP production. Further investigation of mitochondrial function revealed that mild acidosis alleviated OGD-induced collapse of mitochondrial membrane potentials as well as damage to respiratory function, at least in part by reducing impacts on complex I and II activities. Inhibition of complex I activity aggravated neuronal death, which suggests that the contribution of mild acidosis to maintaining complex I activity promoted neuronal survival during OGD. Our findings reveal maintaining mitochondrial respiration as a new possible protective mechanism of mild acidosis during ischemia, on neurons.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.8b00737