Hyperbaric Oxygen Prevents Cognitive Impairments in Mice Induced by D-Galactose by Improving Cholinergic and Antiapoptotic Functions

Our previous study demonstrated that hyperbaric oxygen ( HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging- related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D- galactose ( D- gal)- treated mice. A model of aging was established via systemic intraperitoneal injection of D- gal daily for 8 weeks. HBO was administered during the last 2 weeks of D- gal injection. Our results showed that HBO in D- gal- treated mice significantly improved behavioral performance on the open field test and passive avoidance task. Studies on the potential mechanisms of this effect showed that HBO significantly reduced oxidative stress and blocked the nuclear factor-kappa B pathway. Moreover, HBO significantly increased the levels of choline acetyltransferase and acetylcholine and decreased the activity of acetylcholinesterase in the hippocampus. Furthermore, HBO markedly increased expression of the anti- apoptosis protein Bcl- 2 and glial fibrillary acidic protein meanwhile decreased expression of the pro- apoptosis proteins Bax and caspase- 3. Importantly, there was a significant reduction in expression of A beta- related genes, such as amyloid precursor protein, beta- site amyloid cleaving enzyme- 1 and cathepsin B mRNA. These decreases were accompanied by significant increases in expression of neprilysin and insulin- degrading enzyme mRNA. Moreover, compared with the Vitamin E group, HBO combined with Vitamin E exhibited significant difference in part of the above mention parameters. These findings suggest that HBO may act as a neuroprotective agent in preventing cognitive impairments.