Testosterone Replacement Therapy: Role in Modulating Oxidative Stress within the Entorhinal Cortex

Purpose: Sleep apnea affects approximately a quarter of all Americans, with a higher incidence rate among men. Cognitive impairments are commonly observed. A rat model of sleep apnea, Chronic Intermittent Hypoxia (CIH), exhibits cognitive impairments associated with oxidative stress (OS). The entorhinal cortex (ETC) region of the brain is sensitive to OS and involved in cognition. Our studies show that Testosterone Replacement Therapy (TRT) can protect against CIH-induced circulating OS. However, it is unknown what the impact of TRT is on OS in the ETC. Methods: To address if TRT mitigates OS in the ETC, banked tissue from young adult male F344BN rats were exposed to normoxia (room air) or CIH (8-minute cycles of 5 minutes of 10% O2 and 3 minutes of 21% O2). Rats were gonadally intact, gonadectomized, or gonadectomized with TRT. OS was quantified by protein analysis of calpain cleavage of Spectrin and COX2. Since astrocytes can buffer OS, we quantified a marker of astrocytes (GFAP). Kruskal-Wallis non-parametric statistics were used. Results: Our prior results showed increased circulating OS in CIH exposed rats that were mitigated by TRT. Similarly, CIH increased OS in the ETC. However, astrocytes were increased only in TRT by CIH. Conclusion: This study suggests that TRT decreased OS by increasing astrocytes in the ETC. Astrocytes can play neuroprotective roles in the brain by buffering and neutralizing free radicals that lead to OS. TRT may be useful in preventing cognitive impairment associated with sleep apnea.