Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
Desmoplakin is the components of desmosomes, which are complex structures specialized for cell-to-cell junctions. The expression of desmoplakin in brain is restricted in the dentate gyrus (DG) of the hippocampus. Recent study has suggested that desmoplakin plays an important role in postnatal neurogenesis of the hippocampus. We previously found that the expression of desmoplakin in the adult hippocampus is decreased by antidepressant treatments. However, the role of desmoplakin or the presence of desmosome-like adhesion complex in the hippocampus has remained unknown. In this study, we examined localization of desmoplakin protein in the mature DG and time course of expression change by different types of antidepressant treatments: SSRI fluoxetine and electroconvulsive stimulation. We also explored the role of desmoplakin in the mature DG by knockdown of desmoplakin. Immunohistochemical analysis showed that the expression signals of desmoplakin were found in the cell bodies in the mature granule cells of the DG, suggesting that desmoplakin involves in cell-to-cell adhesion complex in the mature DG. Both of chronic treatment of fluoxetine and repeated electroconvulsive stimulation continuously decreased the expression of desmoplakin in the DG, while a single electroconvulsive stimulation transiently decreased the expression of desmoplakin. We next generated adeno-associated virus (AAV) expressing artificial microRNA targeting desmoplakin, and injected this AAV into the DG. Knockdown of desmoplakin expression in the mature granule neurons was confirmed by immunohistochemical analysis. Knockdown of desmoplakin in the mature DG facilitated the expression of brain-derived neurotrophic factor, BDNF, and suppressed the expression of calbindin, a marker of mature DG neuron, in the hippocampus. Collectively, our findings suggest that suppression of desmoplakin expression in the adult DG by antidepressant treatments activate the neuronal function and modulates the state of maturation.
