OXIDATIVE INJURY OF SYNAPSE AND ALTERATION OF ANTIOXIDATIVE DEFENSE SYSTEMS IN RATS, AND ITS PREVENTION BY VITAMIN-E

In order to define whether active oxygen species actually induce oxida tive damage to the nervous system, and how antioxidative defense syste ms are changed by oxidative stress, morphological and functional chang es in the nervous system and antioxidant status were investigated. Whe n mts were exposed to 100% oxygen in a chamber, many morphological cha nges, e.g. swollen astrocytes around vessels, deformed nuclei in nerve cells, pigmentation, swollen mitochondria, and abnormal accumulation of synaptic vesicles in swollen nerve terminals, were observed by elec tron microscopy. When synaptosomes isolated from oxygen-exposed rats w ere stimulated by KCl, acetylcholine release from the terminal was dec reased more significantly than in synaptosomes from unexposed rats (P< 0.01). Synaptic plasma membrane fluidity decreased in response to oxyg en exposure, and plasma membrane permeability to sucrose was increased significantly (P<0.05). The cholesterol/phospholipid ratio of the pla sma membranes was increased by oxidative stress and the content of uns aturated fatty acids, especially arachidonic acid and docosahexaenoic acid, decreased. The levels of thiobarbituric-acid-reactive substances in the plasma membranes of oxygen-exposed rats were significantly hig her than in unexposed rats (P<0.01). These results suggest that free r adicals derived from oxygen may attack nerve terminals and peroxidize the plasma membrane. It was found that in response to the oxidative st ress, the status of the defense system in synapse, i.e. the concentrat ion of vitamin E, activities of superoxide dismutase and glutathione p eroxidase changed, and that many of the changes observed were reduced remarkably by the intraperitoneal administration of vitamin E prior to stress. Data support the idea that vitamin E contributes to the prote ction against nerve dysfunction caused by oxidative stress.