Hyperbaric oxygen therapy improves cognitive function in D‐galactose‐induced aging via restoring autophagy, apoptosis, microglia activation and synaptic plasticity in hippocampus

Abstract Background Aging is the major risk factor for the age‐related diseases such as dementia and Alzheimer's disease. Previous studies found that aging could impair autophagy, microglia morphology and synaptic plasticity in hippocampus, resulting in cognitive decline. Although there are several models that usually used to induce aging, D‐galactose exposure induced aging as similar patterns as shown in naturally aging. Among the various treatments of Alzeimer’s disease, hyperbaric oxygen therapy (HBOT), which inhales 100 % pure oxygen in a pressurized hyperbaric chamber, becomes the focus of interest because it is a non‐invasive and painless treatment. Previous studies also found that HBOT increased antioxidants, decreased oxidative stress and the number of microglia in Alzheimer’s model. However, the effect of HBOT on autophagy, apoptosis, microglia activation, Alzheimer's protein production, synaptic plasticity and cognitive function in the model of D‐galactose‐induced aging has never been studied. We hypothesize that HBOT decreases oxidative stress, microglia hyperactivation, autophagic impairement, apoptosis, synaptic dysplasticity and cognitive impairment in D‐galactose‐induced aging. Method Fifteen Wistar rats (6‐week‐old) were received either vehicle as control rats (0.9% NSS, s,c; n=5) or D‐galactose as D‐gal rats (150mg/kg/d, s.c; n=10) for 10 weeks. After that, control rats were given sham‐treatment (1ATA, 80L/min, 80mins/day; CS; n=5), D‐gal rats were given together with either sham‐treatment (1ATA, 80L/min, 80mins/day; DS; n=5) or HBOT (2ATA, pure O 2 , 250L/min, 80mins/day; DH; n=5) for 14‐day. Novel object location test and hippocampal pathologies were determined after HBOT. Result We found that D‐gal rats had increased hippocampal oxidative stress, autophagy impairment, BACE1, microglial hyperactivation, apoptosis and synaptic dysplasticity, which resulted in cognitive impairment. Interestingly, HBOT decreased hippocampal oxidative stress, autophagy impairment, BACE1, microglial hyperactivation, apoptosis, synaptic dysplasticity and cognitive impairment in D‐galactose‐induced aging rats (p<0.05, Figure 1). Conclusion HBOT decreased cognitive impairment in D‐galactose‐induced aging via reducing hippocampal oxidative stress, autophagic impairment, BACE1, microglial hyperactivation, apoptosis and synaptic dysplasticity. Therefore, HBOT may be used as a safe and effective treatment to prevent the neurodegeneration of aging.