Type 3 adenylyl cyclase in the main olfactory epithelium participates in depression-like and anxiety-like behaviours.

BACKGROUND

Deficiency of olfaction is thought to be associated with depression, and type 3 adenylyl cyclase (AC) genetic knockout and forebrain knockout mice show depression-like behaviours. AC is expressed in the main olfactory epithelium (MOE) and hippocampus, which plays an important role in olfactory signal transduction. However, it is unclear whether AC in the MOE also plays a role in the pathogenesis of depression. Thus, we aimed to study the relationship between AC in the MOE and the pathogenesis of depression.

METHODS

We obtained anosmic mice by intranasal perfusion of zinc sulphate (ZnSO) (ZnSO mice), and distinctively knocked down AC in the MOE (AC mice) by CRISPR/cas9 technology. Behavioural tests related to depression and anxiety were employed to evaluate the depression- and anxiety-like behaviours of mice. The mRNA and protein expressions of tyrosine hydroxylase (TH), dopamine receptors (Drds), and N-Methyl D-aspartate receptor subunit 2B (GluN2B) in the hippocampus of mice were investigated by qPCR and western blotting to explore the mechanism of depression and anxiety caused by AC in the MOE, preliminarily.

RESULTS

Compared with NaCl mice, ZnSO mice exhibited depression-like behaviours in tail suspension tests (TST), forced swimming tests, and social (FST) interaction tests (SIT), but showed no anxiety-like behaviours in anxiety-related behavioural tests. The mRNA and protein expressions of Drd3 and GluN2B in the hippocampus of ZnSO mice were significantly downregulated. Compared with the negative control mice (NC mice), AC mice showed depression-like behaviours in TST, FST, and SIT tests, anxiety-like behaviours in light/dark transition test, elevated-plus maze test, and novelty-suppressed feeding test. The protein expressions of Drd3, TH, and GluN2B were significantly downregulated in the hippocampus.

LIMITATIONS

We did not further demonstrate that AC in the MOE causes depression through the dopaminergic nervous system with dopamine or dopamine receptor agonists.

CONCLUSIONS

Our data demonstrate that intranasal infusion of ZnSO can cause depression-like behaviours and has no effect on anxiety-like behaviours. Specific knockdown of AC in the MOE can cause depression-like and anxiety-like behaviours. The behavioural changes caused by intranasal ZnSO and specific knockdown of AC in the MOE can be related to the significant downregulation of dopaminergic system and GluN2B expressions in the hippocampus of mice.