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Effect of glycolysis inhibition on mitochondrial function in rat brain
D Cano-Ramírez1, C E Torres-Vargas, S Guerrero-Castillo
1Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510, México, DF, Mexico.
Abstract:
Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.
Insights
Inhibiting glycolysis with iodoacetate in rats caused slight mitochondrial malfunction and oxidative stress in the brain, but did not lead to severe mitochondrial impairment. This suggests a minor impact on neural energy metabolism.
Area of Science:
- Neuroscience
- Biochemistry
- Cellular Biology
Background:
- Glycolysis inhibition increases neural vulnerability to excitotoxicity via unknown mechanisms.
- Mitochondrial failure is a potential, yet unstudied, contributor to this vulnerability in the brain.
Purpose of the Study:
- To investigate the effects of glycolysis inhibition on mitochondrial function and oxidative stress in the rat brain.
- To elucidate the impact of iodoacetate-induced glycolysis inhibition on key mitochondrial parameters.
Main Methods:
- Rats were treated with iodoacetate (25 mg/kg/day for 3 days).
- Mitochondria were isolated from rat brain regions (cortex, striatum, cerebellum).
- Assessed oxygen consumption, ATP synthesis, membrane potential, reactive oxygen species (ROS), lipoperoxidation, glutathione, and aconitase activity.
Main Results:
- Aconitase activity and oxygen consumption were reduced in the brain cortex and striatum.
- Slight mitochondrial malfunction and increased oxidative stress were observed.
- Severe mitochondrial impairment was not detected.
Conclusions:
- Glycolysis inhibition by iodoacetate induces mild mitochondrial dysfunction and oxidative stress in specific brain regions.
- These changes may contribute to, but do not fully explain, the enhanced neural vulnerability to excitotoxicity.
