Expression of Tachykinin 2/Neurokinin B and Neuropeptide Y and the Functional Contribution of Neuropeptide Y in the Mouse Dentate Gyrus following Repeated Electroconvulsive Seizure

Abstract

Electroconvulsive therapy is an effective treatment option for major depression. Studies using rodent electroconvulsive seizure (ECS) models have suggested that the dentate gyrus (DG) of the hippocampal formation is critically involved and that ECS induces robust transcriptomic changes in the DG. Although previous studies have suggested that the expression of two neuropeptide genes, Tachykinin 2 (TAC2) and neuropeptide Y (Npy), is induced by repeated ECS in the DG, the temporal and spatial expression patterns of these genes and their functional contribution to the DG remain unknown. In this study, we found that Tac2 mRNA expression was induced by repeated ECS in the subgranular zone (SGZ), a neurogenic niche, of the DG. In contrast, the expression of Npy mRNA was induced by single and repeated ECS in the hilus. Immunohistochemical analysis revealed that repeated ECS increased the number of NPY-positive cells exhibiting low or undetectable somatostatin expression in the hilus, suggesting the presence of a stimulus-responsive cell population. We further found that the ECS-induced increase in immature neurons in the SGZ was partially suppressed by intracerebroventricular infusion of the NPY-Y1 receptor antagonist, suggesting a modulatory role for NPY-Y1 signaling in ECS-induced neurogenesis. These findings suggest that ECS engages neuropeptide-mediated neuromodulation in a distinct temporal and spatial pattern in the DG.