Androgens modulate chronic intermittent hypoxia effects on brain and behavior

Sleep apnea is associated with testosterone dysregulation as well as increased risk of developing neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). A rodent model of the hypoxemic events of sleep apnea, chronic intermittent hypoxia (CIH), has been previously documented to impair cognitive function and elevate oxidative stress in male rats, while simultaneously decreasing testosterone. Therefore, androgens may modulate neuronal function under CIH. To investigate the role of androgens during CIH, male rats were assigned to one of four hormone groups: 1) gonadally intact, 2) gonadectomized (GDX), 3) GDX + testosterone (T) supplemented, or 4) GDX + dihydrotestosterone (DHT) supplemented. Each group was exposed to either normal room air or CIH exposure for one week, followed by memory and motor task assessments. Brain regions associated with AD and PD (entorhinal cortex, dorsal hippocampus, and substantia nigra) were examined for oxidative stress and inflammatory markers, key characteristics of AD and PD. Gonadally intact rats exhibited elevated oxidative stress due to CIH, but no significant memory and motor impairments. GDX increased memory impairments, regardless of CIH exposure. T preserved memory function and prevented detrimental CIH-induced changes. In contrast, DHT was not protective, as evidenced by exacerbated oxidative stress under CIH. Further, CIH induced significant spatial memory impairment in rats administered DHT. These results indicate androgens can have both neuroprotective and detrimental effects under CIH, which may have clinical relevance for men with untreated sleep apnea.