Univ. Grenoble Alpes, Inserm U1216, GIN, 38000, Grenoble, France.
Univ. Grenoble Alpes, Inserm U1216, GIN, 38000, Grenoble, France; Univ. Grenoble Alpes, CHU Grenoble Alpes, Service Hospitalo Universitaire de Psychiatrie, 38000, Grenoble, France.
Brain Stimul. 2018 Nov-Dec;11(6):1336-1347. doi: 10.1016/j.brs.2018.08.001. Epub 2018 Aug 15.
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.
Unravel biological basis of electroconvulsive stimulation (ECS) efficacy, the animal equivalent of ECT.
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).
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.
Altogether, these results reveal that increased synaptic connectivity and extended neuronal survival are key to the short and long-term efficacy of ECS.
严重且药物难治性精神疾病，如重度抑郁症、双相情感障碍或精神分裂症，可以通过电休克疗法（ECT）有效且快速地治疗。尽管 ECT 已经广泛使用了很长时间，但它的治疗作用的神经生物学机制仍不完全清楚。
阐明电惊厥刺激（ECS）疗效的生物学基础，即 ECT 的动物等效物。
我们使用 MAP6 KO 小鼠，这是一种持续表现出与抑郁症某些方面相关特征的基因模型，分析了单独进行 ECS 治疗（在 2 周内进行 10 次刺激）以及与延续方案相关的 ECS 治疗的行为和生物学后果（每周进行 2 次刺激，持续 5 周）。
ECS 治疗对固有行为缺陷有有益的影响。我们表明，行为改善与治疗前产生的神经元的存活和整合的强烈增加有关。逆转录病毒感染表明，更多整合的神经元表现出增加的树突复杂性和棘密度，以及重塑的突触。此外，我们的研究结果表明，ECS 触发皮质中的突触发生增加。由 ECS 治疗诱导的持续新生神经元存活率与行为改善相关，但在完成 ECS 治疗后 40 天出现复发。然而，在初始 ECS 治疗后进行为期 5 周的延续方案可导致行为的持续改善，这与新生神经元的持续存活率相关。
总之，这些结果表明增加突触连接和延长神经元存活是 ECS 短期和长期疗效的关键。
