Differential Glial Response and Neurodegenerative Patterns in CA1, CA3, and DG Hippocampal Regions of 5XFAD Mice

Abstract

In this study, the distinct patterns of glial response and neurodegeneration within the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus were examined in 5XFAD mice at 6 and 12 months of age. The primary feature of this transgenic mouse model is the rapid onset of amyloid pathology. We employed quantitative assessments via immunohistochemistry, incorporating double staining techniques, followed by observation with light microscopy and subsequent digital analysis of microscopic images. We identified significantly increased Aβ deposition in these three hippocampal regions at 6 and 12 months of transgenic mice. Moreover, the CA1 and CA3 regions showed higher vulnerability, with signs of reactive astrogliosis such as increased astrocyte density and elevated GFAP expression. Additionally, we observed a significant rise in microglia density, along with elevated inflammatory markers (TNFα) in these hippocampal regions. These findings highlight a non-uniform glial and neuronal response to Aβ plaque deposition within the hippocampal regions of 5xFAD mice, potentially contributing to the neurodegenerative and memory deficit characteristics of Alzheimer’s disease in this model.