Journal
BRAIN STIMULATION
Volume 11, Issue 6, Pages 1336-1347Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.brs.2018.08.001
Keywords
ECS; ECT; Adult neurogenesis; MAP6 KO mice; Neuroplasticity; Antidepressant
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Funding
- Inserm
- CEA
- French National Research Agency [2010- Blanc-120201 CBioS]
- Labex GRAL [ANR-10-LABX-49-01]
- Region Rhone-Alpes, Cluster HVN-ARC2
- Proteomics French Infrastructure [ANR-10-INBS-08-01]
- University Grenoble Alpes
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Background: Severe and medication-resistant psychiatric diseases, such as major depressive disorder, bipolar disorder or schizophrenia, can be effectively and rapidly treated by electroconvulsive therapy (ECT). Despite extensive long-standing clinical use, the neurobiological mechanisms underlying the curative action of ECT remain incompletely understood. Objective: Unravel biological basis of electroconvulsive stimulation (ECS) efficacy, the animal equivalent of ECT. Methods: Using MAP6 KO mouse, a genetic model that constitutively exhibits features relevant to some aspects of depression; we analyzed the behavioral and biological consequences of ECS treatment alone (10 stimulations over a 2-week period) and associated with a continuation protocol (2 stimulations per week for 5 weeks). Results: ECS treatment had a beneficial effect on constitutive behavioral defects. We showed that behavioral improvement is associated with a strong increase in the survival and integration of neurons born before ECS treatment. Retroviral infection revealed the larger number of integrated neurons to exhibit increased dendritic complexity and spine density, as well as remodeled synapses. Furthermore, our results show that ECS triggers a cortical increase in synaptogenesis. A sustained newborn neuron survival rate, induced by ECS treatment, is associated with the behavioral improvement, but relapse occurred 40 days after completing the ECS treatment. However, a 5-week continuation protocol following the initial ECS treatment led to persistent improvement of behavior correlated with sustained rate survival of newborn neurons. Conclusion: Altogether, these results reveal that increased synaptic connectivity and extended neuronal survival are key to the short and long-term efficacy of ECS. (C) 2018 The Authors. Published by Elsevier Inc.
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