Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that leads to severe cognitive and functional impairments. Many AD patients also exhibit neuropsychiatric symptoms (NPS) such as anxiety and prior to the clinical diagnosis of dementia. The prodromal manifestation of NPS is highly prevalent among patients with mild cognitive impairment (MCI), and the co-occurrence of preclinical NPS and MCI is associated with an increased risk of developing AD. Prolonged or repeated exposure to stress can result in behavioral disturbances (e.g., anxiety) and accelerated global cognitive decline. Importantly, AD patients exhibit altered stress systems and AD-related neuropathology has been linked to stress in transgenic (Tg+) mice. Collectively, these data suggest that altered stress systems may represent a causal link between NPS and AD. To address this possibility, we examined the effects of chronic stress in adult male TgF344-AD (Tg+) and wildtype (WT) rats for footshock-induced conditioned fear and anxiety-like behavior in the elevated plus-maze (EPM). Results indicated that Tg+ rats display higher levels of anxiety-like behaviors in the EPM compared to WT controls with no differences in general locomotor activity, but these differences are not exacerbated by chronic stress exposure. Additionally, both stressed and non-stressed Tg+ and WT rats exhibited similar levels of fear-related behaviors with no differences in contextual fear learning. Several methodological issues are discussed that may have prevented our ability to detect a stress effect or differences in fear-related behaviors.
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TgF344-AD rat model, Alzheimer's Disease, Chronic Stress, Anxiety, Fear
Bouquin, Samuel James. "Effects of Chronic Stress on Anxiety-like Behavior and Fear Learning in the TgF344-AD Rat Model of Alzheimer’s Disease." (2020). https://digitalrepository.unm.edu/psy_etds/335