Aging and oxidative stress in neurodegeneration.
The effect of oxidative stress on the function of brain synapse, the difference in susceptibility of synapse to hyperoxia with age, and the changes in vitamin E status by stress and aging were investigated. Synaptic membrane permeability to sucrose was increased with age. When rats were subjected to hyperoxia, the membrane permeability on each age increased significantly. The susceptibility of synapse of 25 month old rats exposed to stress was about 2.5 times higher than unexposed old rats. The synaptic plasma membrane fluidity decreased significantly either in response to hyperoxia or during aging. The thiobarbituric acid reactive substances (TBARS) in the synaptic plasma membranes increased with age, and those in the membranes of oxygen-exposed rats were higher than in the unexposed rats. The cholesterol/phospholipids (C/P) ratio of the membranes increased significantly with age, and the values in the membranes of oxygen-exposed rats increased more significantly than in unexposed rats of each age. In a measurement of fatty acid content in the membranes, the content of docosahexaenoic acid (DHA, C22:6) decreased significantly during aging and by hyperoxia. These results suggest that free radicals derived from oxygen may attack nerve terminals and peroxidize the membrane, resulting in the deterioration of function of brain synapse, and that susceptibility of synapse to oxidative stress was significantly increased with age. Vitamin E content in the synaptic plasma membranes decreased with age. When rats were subjected to oxidative stress, the content was lower in each age than in normal rat membranes. An intraperitoneal administration of vitamin E prior to stress reduced these abnormalities. It is obvious that vitamin E contributes to the protection against nerve terminal dysfunction caused by oxidative stress.
Urano
S
S
Department of Biological Chemistry, Faculty of Industrial Chemistry, Shibaura Institute of Technology, Tokyo, Japan.
Sato
Y
Y
Otonari
T
T
Makabe
S
S
Suzuki
S
S
Ogata
M
M
Endo
T
T
D000375:Aging; D000818:Animals; D002463:Cell Membrane Permeability; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008854:Microscopy, Electron; D009410:Nerve Degeneration; D018384:Oxidative Stress; D010100:Oxygen / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013570:Synaptic Membranes / Q000502:physiology / Q000648:ultrastructure; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage
D005227:Fatty Acids; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D004281:Docosahexaenoic Acids; D010100:Oxygen