• KSBNS 2024


Original Article

Exp Neurobiol 2021; 30(6): 415-429

Published online December 31, 2021

© The Korean Society for Brain and Neural Sciences

Hyperoxygenation Ameliorates Stress-induced Neuronal and Behavioral Deficits

Juli Choi1, Hye-Jin Kwon1, Ju-Young Seoh2,3 and Pyung-Lim Han1*

1Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul 03760, 2Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07985, 3Central Research Laboratory, GI Biome, Inc., Seongnam 13201, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-3277-4130, FAX: 82-2-3277-3419

Received: August 15, 2021; Revised: December 22, 2021; Accepted: December 23, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Graphical Abstract

Keywords: Hyperoxygenation, Chronic stress, Mitochondria, Neurogenesis