Date of Award

Spring 5-2026

Language

English

Document Type

Honors Thesis

Degree Name

Bachelor of Arts

Department

Psychology

Advisor/Committee Chair

Damian Zuloaga

Committee Member

Dev K. Dalal

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by a progressive decline in cognitive function. Neuropathologically, AD is shown as cortical intracellular neurofibrillary tangles (NFT) and extracellular β-amyloid (Aβ) plaques (Riverol & Lopez 2011) along with cerebral hypometabolism, neuroinflammation, and neuronal death (Armstrong et al. 2021). There are indications that early to mid-life stress has an impact on the risk of cognitive decline and plays a part in the pathology of the neurodegeneration that comes with AD (Armstrong et al. 2021). Psychological stress contributes to emotional states like depression and anxiety. It has been shown that people with higher levels of stress throughout their lifetime have a higher chance of developing dementia prior to death than those without chronic stress (Wilson, 2007). Sex also plays a role in stress, with female humans having approximately double the number of incidences with disorders such as anxiety and depression, then human men. The amygdala responds to acute stress by activating the fight or flight response and inducing the adrenal gland to release noradrenaline and adrenaline (Armstrong 2021). Higher levels of anxiety and depression are associated with aging, possibly due to decreased amygdala functions; AD is also associated with aging as well as higher rates of anxiety and depression, with this there is evidence that points to the dysregulation of the amygdala and HPA axis in AD (Talarovicova 2007). Longer term stress is regulated by the hypothalamus-pituitary-adrenal (HPA) axis, which stimulates glucocorticoid secretion from the adrenal gland. The hypersecretion of glucocorticoids, due to high levels of stress, has been related to higher levels of anxiety and depression (Zuloaga, 2024). In addition, there are higher levels of glucocorticoids in men with AD, and higher levels of GC secretion is associated with worse cognition and higher amyloid plaque pathology (Zuloaga, 2024), which further implicates the dysregulation of the HPA axis in patients with AD. AD has been associated with high levels of anxiety and depression related to high glucocorticoid release through a dysregulated HPA axis. Chronically high levels of glucocorticoids also create higher levels of cytokine release and neuroinflammation (Yang, 2020), which could implicate the HPA axis in exacerbating AD symptomology and pathology. In addition to the female-leaning sex bias seen in the acquisition of AD, tau levels have been shown to be higher in women than in men with AD (Sundermann, 2020). However, the sex difference between tau levels disappeared when examining testosterone levels as a variable, which has led many to think that testosterone is a protective hormone against the phosphorylation of tau (Sundermann, 2020). The androgen sex steroid DHT is a neuroprotective metabolite of testosterone that has been shown in past studies to exert an anti-inflammatory effect on activated microglia (Yang, 2020). In the current study we are interested in the effects that DHT has on male transgenic mice in modulating the physiological and behavioral stress response. Androgen receptors are one of the ways that the body can regulate the GC secretion levels and protect against neuroinflammation (Zuloaga, 2024) In this study, we used immunohistochemistry to show the effect of DHT and chronic variable stress on stress-induced neural activation and how that affects behavioral responses related to stress. In the current study we looked at the presence or absence of DHT in mice that have been put through a chronic stress paradigm, and through neural activation and grooming behaviors we were able to see the relation that DHT has on male mice with AD and their physiological anxiety and depression activation in different regions of interest in the brain. We hypothesized that the males with DHT would have decreased anxiety and depressive behaviors and decreased neural activation following stress, suggesting that DHT might decrease anxiety and depression in patients with AD.

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