Investigation of the function of desmoplakin in the hippocampus

Abstract

Desmosome is a cell structure of cell-to-cell adhesion in epithelia and cardiac muscles. Desmoplakin, a component of desmosome, is highly expressed in the dentate gyrus (DG) in the brain, although there is no evidence for desmosome structures in neurons. We previously found that the expression of desmoplakin in mouse DG was decreased by antidepressant treatments, including selective serotonin reuptake inhibitors (SSRIs) and electroconvulsive stimulation (ECS), a model of electroconvulsive therapy. However, the role of desmoplakin in hippocampus has been unknown. In this study, we generated adeno associated virus expressing artificial microRNA targeting desmoplakin to suppress desmoplakin expression, and injected it into the mouse DG. We conducted anxiety-like and depressive-like behavioral tests, and examined synaptic potentiation and mature markers expression. Knockdown of desmoplakin in the DG did not affect anxiety-like and depressive-like behaviors. We further found that desmoplakin knockdown decreased synaptic potentiation and increased the mature marker expression in the DG. These results implicate that down-regulation of desmoplakin expression may oppositely affect antidepressant effects in the hippocampus.