Cholesterol: a two-edged sword in brain aging.
Previous research from several laboratories has indicated that cholesterol (CHO) accumulates in neuronal membranes and alters their structural and signal transduction (ST) properties during aging. The possible reasons for these increases in membrane CHO have not been specified. However, present findings suggest that such accumulation may actually serve to protect neuronal tissue from oxidative damage. Striatal slices (6, 24 month rats) were preincubated in 1 mM CHO (30 min) followed by incubation with H2O2 (10 microM, 30 min). The slices were then either superfused with 30 mM KCl in the presence or absence of 500 microM oxotremorine (Ox), and K(+)-evoked dopamine release (K(+)-ERDA) examined or assessed for carbachol-stimulated low K(m) GTPase activity. The results indicated that CHO incubation prior to H2O2 in either age group was effective in preventing H2O2 reductions in both non-Ox-enhanced K(+)-ERDA and Ox conditions, as well as sodium nitroprusside (SNP 150 microM)-induced decreases in K(+)-ERDA. In addition, H2O2-induced deficits in carbachol-stimulated low K(m) GTPase activity were reduced in the striatal tissue from the old animals pretreated with CHO. However, if the slices were incubated in H2O2 prior to CHO exposure, CHO enhanced the H2O2 effects in the tissue from the old animals. Thus, depending upon the order of exposure, CHO functioned to enhance or retard the effects of oxidative stress, in an age-dependent manner.
Joseph
J A
JA
USDA-ARS Human Nutrition Research Center on Aging, Boston, MA 02111, USA.
Villalobos-Molinas
R
R
Denisova
N A
NA
Erat
S
S
Strain
J
J
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D010084:Oxidation-Reduction; D011188:Potassium / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D011506:Proteins; D009569:Nitric Oxide; D002217:Carbachol; D002784:Cholesterol; D006861:Hydrogen Peroxide; D020558:GTP Phosphohydrolases; D005978:Glutathione; D011188:Potassium; D004298:Dopamine