title: Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.
abstract: Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations in brain tissues, especially in the hippocampus. These findings are the first evidence that testosterone depletion makes the brain prone to oxidative injury.
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seongbuk-Gu, Seoul, Korea.
authors.forename: Seung-Wan
authors.initials: SW
authors.lastname: Son
authors.affiliation: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, South Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, South Korea.
authors.forename: Hyeong-Geug
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Dong-Woon
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Health Service Management, Daejeon University, Dong-gu, Daejeon, Korea.
authors.forename: Yo-Chan
authors.initials: YC
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seongbuk-Gu, Seoul, Korea.|Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, South Korea.
authors.forename: Chang-Gue
authors.initials: CG
authors.lastname: Son
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009919:Orchiectomy / Q000009:adverse effects; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000172:deficiency*
chemical_list: D017382:Reactive Oxygen Species; D013739:Testosterone
keywords: corticosterone; neurodegeneration; orchiectomy; oxidative stress; psychological stress; testosterone