High doses of vitamin E improve mitochondrial dysfunction in rat hippocampus and frontal cortex upon aging

We have reported a mitochondrial dysfunction in rat hippocampus and frontal cortex associated with oxidative damage upon aging

Ana Navarro; Manuel J. Bandez; Jose M. Lopez-Cepero; Carmen Gómez; Alberto Boveris

2010

Scholarcy highlights

  • Rat aging from 4 to 12 mo was accompanied by hippocampus and frontal cortex mitochondrial dysfunction, with decreases of 23 to 53% in tissue and mitochondrial respiration and in the activities of complexes I and IV and of mitochondrial nitric oxide synthase
  • We have reported a mitochondrial dysfunction in rat hippocampus and frontal cortex associated with oxidative damage upon aging
  • The dietary supplementation with vitamin E was effective in preventing the decrease in mitochondrial respiration in state 3: at 2.0 and 5.0 g/kg of food, hippocampal mitochondrial respiration was at 92 and 96% of the values for young rats, and frontal cortex mitochondrial respiration was at 90 and 95% of the rates for 4-mo-old rats
  • Hippocampal and frontal cortex mitochondria were more sensitive than whole brain mitochondria to the inhibitory effect of aging and to the restoration due to vitamin E effect
  • Frontal cortex and hippocampal mitochondria show a decreased rate of respiration, especially marked with NAD-dependent substrates, and decreased enzymatic activities of complexes I and IV associated with an increase in the content of oxidation products
  • A silver carbonate solution was used for 1 min at room temperature on floating sections, washed and reduced in neutral 10% formaldehyde followed by gold toning for 10 min followed by hyposulfite fixation and washing
  • The preparations of hippocampal and frontal cortex mitochondria are constituted by a majority of neuronal soma mitochondria with a minor fraction of axonal mitochondria and are highly efficient in identifying a tissue mitochondrial failure associated with a higher content of phospholipid and protein oxidation products
  • High-resolution histochemistry at the level of single mitochondria reveals that 12-mo-old rats have hippocampal dendritic fields with relatively reduced staining intensity for cytochrome oxidase in hippocampus synaptic-rich areas, as described before for mouse brain and in agreement with the reduced cytochrome oxidase activity in hippocampus and frontal cortex

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