Trauma-like exposure alters neuronal apoptosis, Bin1, Fkbp5 and NR2B expression in an amyloid-beta (1-42) rat model of Alzheimer's disease

Neurobiol Learn Mem. 2022 Apr:190:107611. doi: 10.1016/j.nlm.2022.107611. Epub 2022 Mar 12.

Abstract

Post-traumatic stress disorder (PTSD) is a risk factor in the development and progression of Alzheimer's disease (AD), with unclear underlying mechanisms. Recently, we provided data showing the effect of trauma-like stress on Bin1 and Fkbp5 expression in the prefrontal cortex of Aβ(1-42) lesioned animals. This present work sought to expand the study by examining the involvement of the amygdala and hippocampus, in addition to highlighting the role of NR2B in the co-occurrence of trauma-like stress and an Aβ AD-like pathology. Trauma-like condition was induced by exposing the animals to footshocks. Aβ(1-42) was injected into the hippocampus of the animals to induce AD-like pathology. Cognitive functions were assessed in the Morris water maze (MWM) and novel object recognition tests, after which amygdala and hippocampus tissues were harvested for neurochemical analyses. We found that the combination of footshocks and Aβ(1-42) lesion caused a decrease in the number of crossings in the target quadrant of the Morris water maze test, indicating memory deficits. Footshocks caused a further downregulation of Bin1 in the amygdala of Aβ(1-42)-lesioned rats. Prior exposure to footshocks downregulated NR2B in the hippocampus of Aβ(1-42)-lesioned rats. In addition, a combination of footshocks and Aβ(1-42) lesion sustained the upregulation of Fkbp5 in the hippocampus and amygdala. A combination of footshocks and Aβ(1-42) lesion increased neuronal apoptosis in the hippocampus and amygdala. In conclusion, exposure to a trauma-like condition may influence AD-like pathology, leading to exaggerated behavioural and molecular changes in the amygdala and hippocampus.

Keywords: Alzheimer’s disease; Amyloid-beta, Cognition; Apoptosis; Post-traumatic stress disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Hippocampus / metabolism
  • Peptide Fragments / metabolism
  • Rats

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments