The interplay of aryl hydrocarbon receptor/WNT/CTNNB1/Notch signaling pathways regulate amyloid beta precursor mRNA/protein expression and effected the learning and memory of mice

Abstract

The amyloid beta precursor protein (APP) plays a pathophysiological role in the development of Alzheimer’s disease as well as a physiological role in neuronal growth and synaptogenesis. The aryl hydrocarbon receptor (AhR)/WNT/Catenin Beta 1 (CTNNB1)/Notch signaling pathways stamp in many functions, including development and growth of neurons. However, the regulatory role of AhR-/WNT-/CTNNB1-/Notch-induced APP expression and its influence on hippocampal-dependent learning and memory deficits is not clear. Male BALB/C mice received 6-formylindolo[3,2-b]carbazole (an AhR agonist), CH223191(an AhR antagonist), DAPT (an inhibitor of Notch signaling), and XAV-939 (a WNT pathway inhibitor) at a single dose of 100 μg/kg, 1, 5 , and 5 mg/kg of body weight, respectively, via intraperitoneal injection alone or in combination. Gene expression analyses and protein assay were performed on the 7th and 29th days. To assess the hippocampal-dependent memory, all six mice also underwent contextual fear conditioning on the 28th day after treatments. Our results showed that endogenous ligand of AhR has a regulatory effect on APP gene. Also, the interaction of AhR/WNT/CTNNB1 has a positive regulatory effect, but Notch has a negative regulatory effect on the mRNA and protein expression of APP, which have a correlation with mice’s learning skills and memory.

The aryl hydrocarbon receptor maintains antitumor activity of liver resident natural killer cells after partial hepatectomy in C57BL/6J mice

“…Mice received three intravenous injections of 3 mg of FICZ for 1 week before PH. The AhR antagonist, CH223191, was injected intraperitoneally at a single dose of 1 mg/kg of body weight three times for 1 week, based on a previous study 17 …”

From Nucleus to Organs: Insights of Aryl Hydrocarbon Receptor Molecular Mechanisms

“…AHR ligands impact neuronal proliferation, differentiation, and survival and consequently learning skills and memory [ 169 ]. It has been found that AHR modifies its gene expression temporally and spatially in the CNS of mice [ 170 ].…”