Effects of Acute Sepsis on Cellular Dynamics and Amyloid Formation in a Mouse Model of Alzheimer’s Disease

Abstract

Our objective was to investigate how sepsis influences cellular dynamics and amyloid formation before and after plaque formation. As such, APP-mice were subjected to a polymicrobial abdominal infection resulting in sepsis at 2 (EarlySepsis) and 4 (LateSepsis) months of age. Behavior was tested before sepsis and at 5 months of age. We could not detect any short-term memory or exploration behavior alterations in APP-mice that were subjected to Early or LateSepsis. Immunohistochemical analysis revealed a lower area of NeuN+ and Iba1+ signal in the cortex of Late compared with EarlySepsis animals (p = 0.016 and p = 0.01), with an increased astrogliosis in LateSepsis animals compared with WT-Sepsis (p = 0.0028), EarlySepsis (p = 0.0032) and the APP-Sham animals (p = 0.048). LateSepsis animals had larger areas of amyloid compared with both EarlySepsis (p = 0.0018) and APP-Sham animals (p = 0.0024). Regardless of the analyzed markers, we were not able to detect any cellular difference at the hippocampal level between groups. We were able to detect an increased inflammatory response around hippocampal plaques in LateSepsis compared with APP-Sham animals (p = 0.0003) and a decrease of AQP4 signal far from Sma+ vessels. We were able to show experimentally that an acute sepsis event before the onset of plaque formation has a minimal effect; however, it could have a major impact after its onset.

Microglial morphology in the somatosensory cortex across lifespan. A quantitative study

“…In older mice, the proliferation might be an indirect consequence of age‐induced dysfunction of the blood‐brain barrier (BBB) 47 . We know now that BBB changes associated with aged can have also pathological causes such as infections, 48 lifestyle 49,50 or even neurodegenerative pathologies 51 . Regardless of the cause of BBB disruption in the aged cortex, there is an imbalance of molecular transport from the parenchyma to the blood, creating a pro‐inflammatory environment that highlights the need of an increase of microglia density.…”