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Cholesterol: a two-edged sword in brain aging

J A Joseph1, R Villalobos-Molinas, N A Denisova

  • 1USDA-ARS Human Nutrition Research Center on Aging, Boston, MA 02111, USA.

Free Radical Biology & Medicine
|January 1, 1997
PubMed
Summary

Cholesterol accumulation in neuronal membranes may protect against oxidative damage. The order of exposure to cholesterol and hydrogen peroxide influences its protective effects on dopamine release and GTPase activity in aging rats.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Aging Research

Background:

  • Cholesterol accumulates in neuronal membranes during aging, altering structure and signal transduction.
  • The protective role of this cholesterol accumulation against oxidative damage is not well understood.

Purpose of the Study:

  • To investigate the protective effects of cholesterol against oxidative stress in rat striatal slices.
  • To determine if the order of exposure to cholesterol and oxidative agents influences these effects in an age-dependent manner.

Main Methods:

  • Rat striatal slices (young and old) were preincubated with cholesterol, followed by exposure to hydrogen peroxide.
  • Potassium-evoked dopamine release and carbachol-stimulated low Km GTPase activity were assessed.
  • The impact of the preincubation order (cholesterol then H2O2, or H2O2 then cholesterol) was examined.

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Main Results:

  • Cholesterol preincubation protected against hydrogen peroxide-induced reductions in dopamine release and GTPase activity.
  • These protective effects were observed in both young and old rats, and were independent of oxotremorine.
  • When slices were exposed to hydrogen peroxide before cholesterol, cholesterol exacerbated the oxidative damage in older rats.

Conclusions:

  • Cholesterol accumulation can protect neuronal tissue from oxidative stress, particularly when applied before the insult.
  • The effect of cholesterol on oxidative stress is age-dependent and sensitive to the timing of exposure.
  • Findings suggest a complex, context-dependent role for membrane cholesterol in neuronal aging and oxidative defense.