Androgens modulate chronic intermittent hypoxia effects on brain and behavior.

Area of Science:

• Neuroscience
• Endocrinology
• Sleep Medicine

Background:

• Sleep apnea is linked to testosterone changes and neurodegenerative diseases like Alzheimer's (AD) and Parkinson's (PD).
• Chronic intermittent hypoxia (CIH), mimicking sleep apnea, impairs cognition, increases oxidative stress, and lowers testosterone in male rats.

Purpose of the Study:

• To investigate the neuroprotective or detrimental effects of androgens (testosterone and dihydrotestosterone) during CIH exposure.
• To determine if androgens modulate neuronal function and oxidative stress in brain regions affected by AD and PD under CIH conditions.

Main Methods:

• Male rats were gonadectomized (GDX) and supplemented with either testosterone (T) or dihydrotestosterone (DHT), or left intact.
• Animals were exposed to normal air or CIH for one week, followed by cognitive and motor assessments.
• Brain tissues from key regions (entorhinal cortex, hippocampus, substantia nigra) were analyzed for oxidative stress and inflammation.

Main Results:

• CIH increased oxidative stress in intact rats but did not cause significant cognitive or motor deficits.
• GDX worsened memory impairments, irrespective of CIH.
• Testosterone (T) supplementation preserved memory and prevented CIH-induced oxidative stress.
• Dihydrotestosterone (DHT) exacerbated oxidative stress under CIH and induced spatial memory impairment.

Conclusions:

• Androgens exhibit dual roles in neuroprotection and neurotoxicity under CIH, depending on the specific hormone.
• Testosterone may offer neuroprotection against CIH-induced cognitive deficits, relevant for sleep apnea patients.
• Findings highlight the clinical significance of androgen modulation in men with untreated sleep apnea and associated neurological risks.