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Brain Stimul. 2018 Nov - Dec;11(6):1336-1347. doi: 10.1016/j.brs.2018.08.001. Epub 2018 Aug 15.

Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: The essential role of neuronal survival.

Author information

1
Univ. Grenoble Alpes, Inserm U1216, GIN, 38000, Grenoble, France.
2
Univ. Grenoble Alpes, Inserm U1216, GIN, 38000, Grenoble, France; Univ. Grenoble Alpes, CHU Grenoble Alpes, Service Hospitalo Universitaire de Psychiatrie, 38000, Grenoble, France.
3
Univ. Grenoble Alpes, Inserm U1216, GIN, 38000, Grenoble, France; Univ. Grenoble Alpes, CEA, Inserm U1216, BIG-GPC, 38000, Grenoble, France.
4
Univ. Grenoble Alpes, CEA, Inserm, BIG-BGE, 38000, Grenoble, France.
5
Univ. Aix-Marseille, INSERM U1249, Institut de Neurobiologie de La Méditerranée, Parc Scientifique de Luminy, 13273, Marseille, France.
6
Univ. Grenoble Alpes, Inserm U1216, GIN, 38000, Grenoble, France; Univ. Grenoble Alpes, CEA, Inserm U1216, BIG-GPC, 38000, Grenoble, France. Electronic address: annie.andrieux@univ-grenoble-alpes.fr.
7
INSERM, U1028, CNRS, UMR5292, Lyon Neuroscience Research Center, Psychiatric Disorders: from Resistance to Response Team, Lyon, F-69000, France; University Lyon 1, Villeurbanne, F-69000, France.
8
Univ. Grenoble Alpes, Inserm U1216, GIN, 38000, Grenoble, France. Electronic address: sylvie.gory-faure@univ-grenoble-alpes.fr.

Abstract

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.

KEYWORDS:

Adult neurogenesis; Antidepressant; ECS; ECT; MAP6 KO mice; Neuroplasticity

PMID:
30146428
DOI:
10.1016/j.brs.2018.08.001
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