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Elevated Testosterone Level and Urine Scent Marking in Male 5xFAD Alzheimer Model Mice
Lisa Gadomsky1, Malena Dos Santos Guilherme1, Jakob Winkler2
1Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg- University, Mainz, Germany.
Background:
Function of the Amyloid Precursor Protein (AβPP) and its various cleavage products still is not unraveled down to the last detail. While its role as a source of the neurotoxic Amyloid beta (Aβ) peptides in Alzheimer's Disease (AD) is undisputed and its property as a cell attachment protein is intriguing, while functions outside the neuronal context are scarcely investigated. This is particularly noteworthy because AβPP has a ubiquitous expression profile and its longer isoforms, AβPP750 and 770, are found in various tissues outside the brain and in non-neuronal cells.
Objective:
Here, we aimed at analyzing the 5xFAD Alzheimer's disease mouse model in regard to male sexual function. The transgenes of this mouse model are regulated by Thy1 promoter activity and Thy1 is expressed in testes, e.g. by Sertoli cells. This allows speculation about an influence on sexual behavior.
Methods:
We analyzed morphological as well as biochemical properties of testicular tissue from 5xFAD mice and wild type littermates and testosterone levels in serum, testes and the brain. Sexual behavior was assessed by a urine scent marking test at different ages for both groups.
Results:
While sperm number, testes weight and morphological phenotypes of sperms were nearly indistinguishable from those of wild type littermates, testicular testosterone levels were significantly increased in the AD model mice. This was accompanied by elevated and prolonged sexual interest as displayed within the urine scent marking test.
Conclusion:
We suggest that overexpression of AβPP, which mostly is used to mimic AD in model mice, also affects male sexual behavior as assessed additional by the Urine Scent Marking (USM) test. The elevated testosterone levels might have an additional impact on central nervous system androgen receptors and also have to be considered when assessing learning and memory capabilities.
Insights
Alzheimer
Area of Science:
- Neuroscience
- Endocrinology
- Reproductive Biology
Background:
- The function of Amyloid Precursor Protein (AβPP) is not fully understood, especially outside the brain.
- AβPP is ubiquitously expressed and its longer isoforms are found in non-neuronal tissues.
- Alzheimer's Disease (AD) models often involve AβPP overexpression, but non-neuronal effects are understudied.
Purpose of the Study:
- To investigate the impact of AβPP overexpression in a mouse model of Alzheimer's Disease on male sexual function.
- To analyze testicular properties and sexual behavior in 5xFAD mice compared to wild-type littermates.
Main Methods:
- Analysis of testicular morphology and biochemistry in 5xFAD and wild-type mice.
- Measurement of testosterone levels in serum, testes, and brain.
- Assessment of sexual behavior using a urine scent marking test at various ages.
Main Results:
- No significant differences in sperm count, testes weight, or sperm morphology were observed.
- Testicular testosterone levels were significantly elevated in 5xFAD mice.
- 5xFAD mice exhibited increased and prolonged sexual interest in the urine scent marking test.
Conclusions:
- AβPP overexpression, used to model AD, influences male sexual behavior.
- Elevated testosterone levels in AD model mice may affect central nervous system androgen receptors.
- These findings suggest potential impacts on learning and memory assessment in AD models.
