Hyperoxygenation Ameliorates Stress-induced Neuronal and Behavioral Deficits

Hyperoxygenation therapy remediates neuronal injury and improves cognitive function in various animal models. In the present study, the optimal conditions for hyperoxygenation treatment of stress-induced maladaptive changes were investigated. Mice exposed to chronic restraint stress (CRST) produce persistent adaptive changes in genomic responses and exhibit depressive-like behaviors. Hyperoxygenation treatment with 100% O₂ (HO₂) at 2.0 atmospheres absolute (ATA) for 1 h daily for 14 days in CRST mice produces an antidepressive effect similar to that of the antidepressant imipramine. In contrast, HO₂ treatment at 2.0 ATA for 1 h daily for shorter duration (3, 5, or 7 days), HO₂ treatment at 1.5 ATA for 1 h daily for 14 days, or hyperbaric air treatment at 2.0 ATA (42% O₂) for 1 h daily for 14 days is ineffective or less effective, indicating that repeated sufficient hyperoxygenation conditions are required to reverse stress-induced maladaptive changes. HO₂ treatment at 2.0 ATA for 14 days restores stress-induced reductions in levels of mitochondrial copy number, stress-induced attenuation of synaptophysin-stained density of axon terminals and MAP-2-staining dendritic processes of pyramidal neurons in the hippocampus, and stress-induced reduced hippocampal neurogenesis. These results suggest that HO₂ treatment at 2.0 ATA for 14 days is effective to ameliorate stress-induced neuronal and behavioral deficits.