Chronic stress leads to earlier cognitive decline in an Alzheimer's mouse model: The role of neuroinflammation and TrkB.

Abstract

While most Alzheimer's disease (AD) studies focus on the cognitive aspects of the disease, less focus is given to affective symptoms. In this study, we investigated the long-term consequences of exposure to chronic stress. 5xFAD AD model mice were exposed to unpredictable chronic mild stress, and cognitive and emotional aspects were examined at 3-time points (up to 4 months after exposure to stress). We found that exposure to chronic stress accelerates neuropathology outcomes in the 5xFAD mouse model in adulthood, accompanied by changes in the neurotrophic system. Specifically, we found that chronic stress accelerated the appearance of short-term spatial memory deficits in the 5xFAD mice and decreased tyrosine kinase B full receptor (TrkB.FL) expression levels. In vitro, we showed that corticosterone impairs the ability of microglia to uptake Aβ and reduces microglial activation. To conclude, our study may shed light on the mechanisms through which mild chronic stress might contribute to the onset and progression of Alzheimer's disease symptoms.