Department of Psychiatry, Yale University, New Haven, CT 06508, USA.
Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11378-83. doi: 10.1073/pnas.1201191109. Epub 2012 Jun 25.
Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressant treatment reverses this effect. We also show that viral-mediated expression of neuritin in the hippocampus produces antidepressant actions and prevents the atrophy of dendrites and spines, as well as depressive and anxiety behaviors caused by CUS. Conversely, neuritin knockdown produces depressive-like behaviors, similar to CUS exposure. The ability of neuritin to increase neuroplasticity is confirmed in models of learning and memory. Our results reveal a unique action of neuritin in models of stress and depression, and demonstrate a role for neuroplasticity in antidepressant treatment response and related behaviors.
海马体神经元树突分支和可塑性的减少，海马体是与情绪障碍有关的边缘结构，被认为是导致抑郁症状的原因。然而，这种影响的机制以及抗抑郁治疗的作用仍未得到充分描述。在这里，我们发现，神经调节素（一种调节神经元可塑性的活性依赖性基因）在海马体中的表达在慢性不可预测的应激（CUS）下减少，而抗抑郁治疗则逆转了这种效应。我们还发现，在海马体中通过病毒介导表达神经调节素可产生抗抑郁作用，并防止由 CUS 引起的树突和棘突萎缩以及抑郁和焦虑行为。相反，神经调节素的敲低会产生类似 CUS 暴露的抑郁样行为。神经调节素增加神经可塑性的能力在学习和记忆模型中得到了证实。我们的研究结果揭示了神经调节素在应激和抑郁模型中的独特作用，并证明了神经可塑性在抗抑郁治疗反应和相关行为中的作用。
