Differential effects of chronic stress on anxiety-like behavior and contextual fear conditioning in the TgF344-AD rat model of Alzheimer's disease

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, such as anxiety and depression, prior to the clinical diagnosis of dementia. Chronic stress is associated with numerous adverse health consequences and disease states, and AD patients exhibit altered stress systems. Thus, stress may represent a causal link between neuropsychiatric symptoms and AD. To address this possibility, we examined the effects of chronic stress in the TgF344-AD rat model that co-expresses the mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1 Delta E9) genes. Adult male transgenic (Tg+) and wild-type (WT) rats (6-7.5 months of age), with and without a history of chronic restraint stress, were tested for footshock-induced conditioned fear and for anxiety-like behavior in the elevated plus-maze. We found that non-stressed Tg+ rats showed increased anxiety-like behavior compared to non-stressed WT rats. In contrast, Tg+ and WT rats did not differ in levels of freezing immediately following footshock or during contextual re-exposure. Additionally, stressed Tg+ rats were not significantly different from stressed WT rats on any measures of anxiety or fear. Thus, while stress has been linked as a risk factor for AD-related pathology, it appears from the present findings that two weeks of daily restraint stress did not further enhance anxiety- or fear-like behaviors in TgF344-AD rats.

Automated summary

Alzheimer's disease is a progressive neurodegenerative disorder associated with cognitive and functional impairments. Chronic stress has been linked as a risk factor for AD-related pathology, but a study found that two weeks of daily restraint stress did not further enhance anxiety- or fear-like behaviors in TgF344-AD rats.