Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression

作者：Schloesser Robert J; Orvoen Sophie; Jimenez Dennisse V; Hardy Nicholas F; Maynard Kristen R; Sukumar Mahima; Manji Husseini K; Gardier Alain M; David Denis J; Martinowich Keri^*

来源：Brain Stimulation, 2015, 8(5): 862-867.

DOI：10.1016/j.brs.2015.05.011

• ECT
• ECS
• Hippocampus
• Neurogenesis
• Neuroplasticity
• Antidepressant

Background: Neurogenesis continues throughout life in the hippocampal dentate gyrus. Chronic treatment with monoaminergic antidepressant drugs stimulates hippocampal neurogenesis, and new neurons are required for some antidepressant-like behaviors. Electroconvulsive seizures (ECS), a laboratory model of electroconvulsive therapy (ECT), robustly stimulate hippocampal neurogenesis. Hypothesis: ECS requires newborn neurons to improve behavioral deficits in a mouse neuroendocrine model of depression.
Methods: We utilized immunohistochemistry for doublecortin (DCX), a marker of migrating neuroblasts, to assess the impact of Sham or ECS treatments (1 treatment per day, 7 treatments over 15 days) on hippocampal neurogenesis in animals receiving 6 weeks of either vehicle or chronic corticosterone (CORT) treatment in the drinking water. We conducted tests of anxiety-and depressive-like behavior to investigate the ability of ECS to reverse CORT-induced behavioral deficits. We also determined whether adult neurons are required for the effects of ECS. For these studies we utilized a pharmacogenetic model (hGFAPtk) to conditionally ablate adult born neurons. We then evaluated behavioral indices of depression after Sham or ECS treatments in CORT-treated wild-type animals and CORT-treated animals lacking neurogenesis.
Results: ECS is able to rescue CORT-induced behavioral deficits in indices of anxiety-and depressive-like behavior. ECS increases both the number and dendritic complexity of adult-born migrating neuroblasts. The ability of ECS to promote antidepressant-like behavior is blocked in mice lacking adult neurogenesis.
Conclusion: ECS ameliorates a number of anxiety-and depressive-like behaviors caused by chronic exposure to CORT. ECS requires intact hippocampal neurogenesis for its efficacy in these behavioral indices.

• 出版日期2015-10