Aging is a major risk factor for Alzheimer's disease (AD), a condition affecting approximately 6.2 million people in the USA. Currently, approved treatments of AD only manage symptoms, therefore it is important to seek out new therapeutics that can reverse and/or slow down the progression of this devastating disease. Hyperbaric Oxygen Therapy (HBOT), an intervention that has been used safely for conditions such as wound healing and decompression sickness, has now been associated with improved brain function in neurological conditions like stroke. HBOT benefits on brain function may be related to reduction in oxidative stress and inflammation, which play a large role in AD pathogenesis. Furthermore, HBOT altered the regulation of 8101 genes in human microvascular endothelial cell. The goal of our study was to determine the viability of HBOT as an intervention in a severe model of AD and identify the underlying mechanisms associated with the expected benefits. Male and female 5xFAD and wildtype (WT) mice were randomly assigned to one of four experimental groups consisting of WT-HBOT, WT+HBOT, 5xFAD-HBOT and 5xFAD+HBOT. HBOT daily (5 days/week) was started at 9-10 months and continued until the mice were euthanized at 12-13 months. Behavioral tests were carried out at 1 month into the treatment with HBOT. Brain regions, namely hippocampus and cortex, were isolated upon euthanization, and saved for future biochemical/molecular evaluations. Differential sex outcomes were found in the cognitive task, in which HBOT improved spatial learning and memory in males only and improved cognitive flexibility in females only. Furthermore, our preliminary data suggest that HBOT moderately affected global DNA methylation in the hippocampus. This work demonstrates that HBOT reverses cognitive impairment associated with an AD phenotype and affected epigenetic changes. Future work will continue to evaluate the underlying mechanisms associated with the beneficial outcomes of HBOT on brain function.
