Anxiety-like but not despair-like behaviors are further aggravated by chronic mild stress in the early stages of APP_swe/PS1dE9 transgenic mice

Abstract

Early Alzheimer's disease (AD) and depression share many symptoms, thus it is very difficult to initially distinguish one from the other.Therefore, characterizing the shared and different biological changes between the two disorders will be helpful in making an early diagnosis and planning treatment. In the present study, 8-week-old APP swe /PS1dE9 transgenic mice received chronic mild stress (CMS) for 8 weeks followed by a series of behavioral, biochemical and pathological analyses.APPswe/PS1dE9 mice demonstrated despair-and anxiety-like behaviors, and reduced sociability, accompanied by high levels of soluble beta-amyloid, glial activation, neuroinflammation and brain derived neurotrophic factor signaling disturbance in the hippocampus. Notably, APPswe/PS1dE9 mice exposure to CMS further aggravated anxiety-like behaviors rather than hopelessness and sociability deficits, accompanied with more severe neuroinflammation, and low serum corticosterone increased to the normal level. These results may help to understand the pathogenic mechanism of psychiatric symptoms associated with early AD.

Activation of PPARA-mediated autophagy reduces Alzheimer disease-like pathology and cognitive decline in a murine model

“…The exact reason for the discrepancy between our study and previous reports [67][68][69][70][71] remained to be determined, but different evaluation platforms and detection time points might be an explanation from the technical point of view. In addition, we noticed that a recent study also showed that APP-PSEN1ΔE9 mice had increased anxiety at the age of 24 weeks [73]. Third, administration of gemfibrozil and Wy14643 led to a recruitment of astrocytes and microglia to the vicinity of amyloid plaques in coronal section of APP-PSEN1ΔE9 mouse brains, and enhanced Aβ clearance via autophagy.…”