Awakening the dormant: Role of axonal guidance cues in stress-induced reorganization of the adult prefrontal cortex leading to depression-like behavior.

Major depressive disorder (MDD) is a chronic and disabling disorder affecting roughly 280 million people worldwide. While multiple brain areas have been implicated, dysfunction of prefrontal cortex (PFC) circuitry has been consistently documented in MDD, as well as in animal models for stress-induced depression-like behavioral states. During brain development, axonal guidance cues organize neuronal wiring by directing axonal pathfinding and arborization, dendritic growth, and synapse formation. Guidance cue systems continue to be expressed in the adult brain and are emerging as important mediators of synaptic plasticity and fine-tuning of mature neural networks. Dysregulation or interference of guidance cues has been linked to depression-like behavioral abnormalities in rodents and MDD in humans. In this review, we focus on the emerging role of guidance cues in stress-induced changes in adult prefrontal cortex circuitry and in precipitating depression-like behaviors. We discuss how modulating axonal guidance cue systems could be a novel approach for precision medicine and the treatment of depression.

重度抑郁症（MDD）是一种慢性致残性疾病，全球约有2.8亿人受其影响。虽然涉及多个脑区，但在MDD以及应激诱导的抑郁样行为状态的动物模型中，前额叶皮质（PFC）回路的功能障碍一直都有记载。在大脑发育过程中，轴突导向因子通过引导轴突寻路和分支、树突生长以及突触形成来组织神经元连接。导向因子系统在成年大脑中继续表达，并逐渐成为突触可塑性和成熟神经网络微调的重要介质。导向因子的失调或干扰与啮齿动物的抑郁样行为异常以及人类的MDD有关。在这篇综述中，我们重点关注导向因子在应激诱导的成年前额叶皮质回路变化以及引发抑郁样行为中的新兴作用。我们讨论了调节轴突导向因子系统如何可能成为精准医学和抑郁症治疗的一种新方法。