|
author |
Angelo C. Angione
| title |
In Vitro Exploration of Androgen Receptor Mediated Neuroprotection of Testosterone in an Oxidative Stress Model of Alzheimer's Disease
| abstract |
Alzheimer's disease (AD) is a neurodegenerative disorder commonly understood
to be affected by age, oxidative stress, Tau hyperphosphorylation and β-Amyloid plaques.
Recent literature has begun to explore the impact of the sex hormones on neuron
resistance to oxidative stress, and the impact that those hormones have on neuron
viability under Alzheimer's disease like conditions. The literature surrounding this
hypothesis has been largely focused on the impacts of estradiol, and research into the
effects of testosterone is sparing. This study aims to build upon the literature exploring
testosterone's in vitro neuroprotective effects. These experiments explored testosterone's
impact on neuron viability and morphology under the Ferrous-Amlyoid-Butionine (FAB)
in vitro cell model of AD. This model system generates reactive oxygen species, which
cause oxidative stress on neurons and is an integral component of sporadic AD. Neuron
viability and morphology changes were analyzed via MTS and immunocytochemistry.
Our findings indicate that testosterone caused an increase in cell metabolism in
unstressed cells, and that it promoted neurons to group together in culture more
frequently. Testosterone had no significant effect on cells when stressed with FAB, and
the clustered pattern of cells was still observed in stressed cells. We further attempted to
assess the pathway by which the actions of testosterone occur by inhibiting the estrogen
receptor with tamoxifen. No significant change in cell viability was observed as a result
of tamoxifen treatment. Cotreatment of neurons with testosterone and tamoxifen resulted
in a statistically significant rescue of cell viability, suggesting that androgen receptor
activation results in neuroprotection from oxidative stress and β-Amyloid. These
experiments, when considered with the broader literature, show that testosterone is
involved in neuroprotective pathways in neurons. Clinically, this suggests that the loss of
testosterone may play an important role in the incidence and pathology of AD in aging
men.
| school |
The College of Liberal Arts, Drew University
| degree |
B.S. (2021)
|
advisor |
Roger Knowles
|
committee |
Graham Cousens Adam Cassano
|
full text | ACAngione.pdf |
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