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

Abstract

Sleep apnea affects approximately a quarter of all Americans. The effects of sleep apnea involve a decrease in testosterone levels, along with an increased rate of hypertension, stroke, and coronary heart disease. Chronic Intermittent Hypoxia (CIH) has also been shown to increase aging and negatively affect cognitive function, as seen with increased oxidative stress within the Entorhinal Cortex. However, it is unknown if Testosterone Replacement Therapy (TRT) can ameliorate the impact of CIH on the entorhinal cortex, which could have significant therapeutic impacts on sleep apnea related cognitive impairment. We hypothesized that TRT would mitigate protein levels of oxidative stress and inflammation, as measured by COX2, GFAP, and Calpain enzymatic activity. Banked brain tissue from young (3 month) F344/BN F1 hybrid male rats were used. Rats were separated into three treatment groups: gonadally intact, gonadectomized (GDX), and GDX with TRT. Then rats were either exposed to room air (normoxic conditions) or CIH for 8 days. Our results showed that neither TRT nor CIH impacted inflammation and oxidative stress related proteins in the entorhinal cortex. However, rats that were exposed to isoflurane anesthesia (GDX and GDX+TRT) showed neuroinflammation. Cognitive impairment has been associated with isoflurane related surgeries. However, the mechanism is unknown, though based on the data inflammation may be involved in isoflurane induced cognitive impairment in surgical patients.