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

Author:

Keshavarzi Majid12,Moradbeygi Fatemeh1,Mobini Keivan1,Ghaffarian Bahraman Ali13,Mohammadi Parisa2,Ghaedi Afsaneh1,Mohammadi-Bardbori Afshin1ORCID

Affiliation:

1. Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 7146864685, Iran

2. Department of Environmental Health, Faculty of Health, Sabzevar University of Medical Sciences, Sabzevar 7146864685, Iran

3. Occupational Environment Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Abstract

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.

Funder

Shiraz University of Medical Sciences

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Toxicology

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