Vulnerability of calbindin, calretinin and parvalbumin in a transgenic/knock-in APPswe/PS1dE9 mouse model of Alzheimer disease together with disruption of hippocampal neurogenesis.

摘要: Abstract The pathogenesis of Alzheimer disease (AD) is characterized by accumulation β-amyloid protein in the brain (in both soluble and insoluble forms) presence intracellular neurofibrillary tangles (NFTs), leading to neurotoxicity. exact mechanisms whereby Aβ triggers alterations are unclear. However, accumulating evidence suggests that a deregulation Ca2 + signaling may play major role progression. Calcium-buffering proteins, including calbindin-D28K (CB), calretinin (CR) parvalbumin (PV), offer neuroprotection maintaining calcium homeostasis. Although marked reductions these proteins have been observed brains mice humans with AD, their contribution AD pathology remains aim present study was analyze distribution patterns CB+, CR+ PV+ interneurons different areas hippocampus, region severely affected AD. A transgenic knock-in APPswe/PS1dE9 mouse model familial used. data were obtained from 3- 12-month-old animals. These ages roughly correspond an early mature adult (prior clinical manifestations) late middle-age (clinical symptoms readily detectable) phase human patients. Immunostaining revealed increases CB PV immunoreactivity (IR) hippocampus 3-month-old mice, compared wild-type Possibly, upregulated attempt control cellular homeostasis synaptic plasticity. pattern CB-IR reversed animals, potentially indicating loss capacity respond pathophysiological processes. In addition, at this age, noticeable increase PV-IR observed, suggesting hippocampal network hyperactivity older AD-like mice. Our results indicate CaBP+ neuronal subpopulations neurogenesis pathology, particularly stages, neurons serve as potential predictors future non-demented individuals.