Abstract
Hippocampal plasticity is hypothesized to play a role in the etiopathogenesis of depression and the antidepressant effect of medications. One form of plasticity that is unique to the hippocampus and is involved in depression-related behaviors in animal models is adult neurogenesis. While chronic electroconvulsive shock (ECS) strongly promotes neurogenesis, less is known about its acute effects and little is known about the neurogenic effects of other forms of stimulation therapy, such as repetitive transcranial magnetic stimulation (rTMS). Here, we investigated the time course of acute ECS and rTMS effects on markers of cell proliferation and neurogenesis in the adult hippocampus. Mice were subjected to a single session of ECS, 10 Hz rTMS (10–rTMS), or intermittent theta burst stimulation (iTBS). Mice in both TMS groups were injected with BrdU 2 days before stimulation to label immature cells. One, 3, or 7 days later, hippocampi were collected and immunostained for BrdU + cells, actively proliferating PCNA + cells, and immature DCX + neurons. Following ECS, mice displayed a transient increase in cell proliferation at 3 days post-stimulation. At 7 days post–stimulation there was an elevation in the number of proliferating neuronal precursor cells (PCNA + DCX +), specifically in the ventral hippocampus. iTBS and rTMS did not alter the number of BrdU + cells, proliferating cells, or immature neurons at any of the post-stimulation time points. Our results suggest that neurostimulation treatments exert different effects on hippocampal neurogenesis, where ECS may have greater neurogenic potential than iTBS and 10–rTMS.
Highlights
Adult hippocampal neurogenesis provides a source of cellular and synaptic plasticity that may be relevant for treating a number of psychiatric disorders [1]
PCNA cell densities did not differ along the dorsoventral axis
To determine whether Electroconvulsive shock (ECS) alters the proliferation of neuronal precursors, we quantified the proportion of PCNA + cells that expressed the immature neuronal marker DCX
Summary
Adult hippocampal neurogenesis provides a source of cellular and synaptic plasticity that may be relevant for treating a number of psychiatric disorders [1]. A considerable amount of this work has been performed in the context of depression since there is hippocampal atrophy in patients [2], reduced neurogenesis in preclinical animal models [3,4], and manipulations that impair or enhance neurogenesis lead to greater or reduced levels of depression-like behavior in mice, respectively [5,6,7]. Given these relationships between neurogenesis and the depressive phenotype, a fundamental question is how neurogenesis can be enhanced to treat depression. The antidepressant-like effects of ECS depend on intact hippocampal neurogenesis [18]
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