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-κB 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 Aβ-related genes, such as
amyloid precursor
protein, β-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.