Abstract Title

Testosterone in the bedroom - not always good

Presenter Name

Brina Snyder

RAD Assignment Number

104

Abstract

Purpose: There are no effective therapeutics to prevent the progression of neurodegenerative diseases, such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). This deficit highlights the need to identify early contributors to neurodegenerative pathophysiology, such as examining common comorbidities. One such comorbidity is sleep apnea. To examine the relationship between sleep apnea and neurodegeneration, we used a rodent model of chronic intermittent hypoxia (CIH) to simulate the hypoxic events experienced by patients with sleep apnea. Interestingly, in male rats CIH causes an increase in oxidative stress (OS) and inflammation, along with a decrease in circulating testosterone (T). Currently, studies have been equivocal about the role of the major male sex hormone, T, in neuroprotection and neurodegeneration. It has been proposed that an OS environment may predispose T to be neurotoxic via androgen receptor activation.

Methods: To address if OS is the switch for testosterone’s neuroprotective or neurotoxic actions, male Long-Evans rats were assigned to different hormone groups: gonadally intact, gonadectomized (GDX), GDX + T (TRT) or GDX + dihydotestosterone (DHT). DHT is an androgen receptor agonist metabolized from T. Two weeks after hormone replacement, rats were exposed to CIH or room air (AHI = 8) for 12 days. During the last 5 days of CIH, cognitive and motor behavioral tests were conducted.

Results: As expected, elevated OS as well as spatial memory and fine motor impairments were observed in response to CIH in gonadally intact rats. This suggests CIH-induced OS results in behavioral deficits associated with early-stages of neurodegenerative diseases. GDX rats exhibited only cognitive impairments, regardless of CIH exposure, indicating sex hormones play a role in memory. Irrespective of CIH exposure, TRT prevented OS generation as well as motor and cognitive impairments. Interestingly, CIH induced OS and cognitive impairments were exacerbated in DHT male rats, compared to gonadally intact rats.

Conclusions: These results indicate that the androgen receptor is involved in T’s negative effects in an OS environment. Since sleep apnea is a common comorbidity of neurodegeneration, the observed sex differences may be due to a negative interaction between OS and androgen receptor activation. Therefore, men with sleep apnea who have elevated OS may be susceptible to neurodegenerative pathophysiology.

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Research Area

Aging/Alzheimer's Disease

Presentation Type

Poster

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Testosterone in the bedroom - not always good

Purpose: There are no effective therapeutics to prevent the progression of neurodegenerative diseases, such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). This deficit highlights the need to identify early contributors to neurodegenerative pathophysiology, such as examining common comorbidities. One such comorbidity is sleep apnea. To examine the relationship between sleep apnea and neurodegeneration, we used a rodent model of chronic intermittent hypoxia (CIH) to simulate the hypoxic events experienced by patients with sleep apnea. Interestingly, in male rats CIH causes an increase in oxidative stress (OS) and inflammation, along with a decrease in circulating testosterone (T). Currently, studies have been equivocal about the role of the major male sex hormone, T, in neuroprotection and neurodegeneration. It has been proposed that an OS environment may predispose T to be neurotoxic via androgen receptor activation.

Methods: To address if OS is the switch for testosterone’s neuroprotective or neurotoxic actions, male Long-Evans rats were assigned to different hormone groups: gonadally intact, gonadectomized (GDX), GDX + T (TRT) or GDX + dihydotestosterone (DHT). DHT is an androgen receptor agonist metabolized from T. Two weeks after hormone replacement, rats were exposed to CIH or room air (AHI = 8) for 12 days. During the last 5 days of CIH, cognitive and motor behavioral tests were conducted.

Results: As expected, elevated OS as well as spatial memory and fine motor impairments were observed in response to CIH in gonadally intact rats. This suggests CIH-induced OS results in behavioral deficits associated with early-stages of neurodegenerative diseases. GDX rats exhibited only cognitive impairments, regardless of CIH exposure, indicating sex hormones play a role in memory. Irrespective of CIH exposure, TRT prevented OS generation as well as motor and cognitive impairments. Interestingly, CIH induced OS and cognitive impairments were exacerbated in DHT male rats, compared to gonadally intact rats.

Conclusions: These results indicate that the androgen receptor is involved in T’s negative effects in an OS environment. Since sleep apnea is a common comorbidity of neurodegeneration, the observed sex differences may be due to a negative interaction between OS and androgen receptor activation. Therefore, men with sleep apnea who have elevated OS may be susceptible to neurodegenerative pathophysiology.