Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers
Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers
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DOI：
10.1523/jneurosci.1309-11.2011
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发表时间：
2011-09-07
影响因子：
5.3
通讯作者：
Becker, Chrystel
中科院分区：
文献类型：
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作者：
Blugeot, Aurelie;Rivat, Cyril;Becker, Chrystel
压力事件增加了以后生活中患抑郁症的风险，但可能的诱发因素仍然未知。我们的研究旨在描述成年动物抑郁症发展的潜在脆弱性特征。在引发应激事件后四周，所有动物的血清皮质酮浓度恢复到对照值，而其他生物学参数仅58%的动物（称为非脆弱性）恢复到基础水平。与此相反，42%的动物表现出持续下降的血清和海马BDNF浓度，减少海马体积和神经发生，CA 3树突回缩和减少的棘密度，以及杏仁核神经元肥大，构成潜在的脆弱性特征抑郁症。在这组被称为脆弱的动物中，随后的轻度应激诱发了血清皮质酮水平的上升和“抑郁”表型，与非脆弱动物相反。脑室内给药7，8-二羟基黄酮，一种选择性TrkB受体激动剂，抑制了“抑郁”表型的发展。因此，我们的研究结果表征了抑郁症出现的潜在脆弱性特征的存在，并确定了低BDNF与正常皮质酮血清浓度的关联作为抑郁症易感性的预测生物标志物。
A stressful event increases the risk of developing depression later in life, but the possible predisposing factors remain unknown. Our study aims to characterize latent vulnerability traits underlying the development of depressive disorders in adult animals. Four weeks after a priming stressful event, serum corticosterone concentration returned to control values in all animals, whereas the other biological parameters returned to basal level in only 58% of animals (called nonvulnerable). In contrast, 42% of animals displayed persistent decreased serum and hippocampus BDNF concentrations, reduced hippocampal volume and neurogenesis, CA3 dendritic retraction and decrease in spine density, as well as amygdala neuron hypertrophy, constituting latent vulnerability traits to depression. In this group, called vulnerable, a subsequent mild stress evoked a rise of serum corticosterone levels and a "depressive" phenotype, in contrast to nonvulnerable animals. Intracerebroventricular administration of 7,8-dihydroxyflavone, a selective TrkB receptor agonist, dampened the development of the "depressive" phenotype. Our results thus characterize the presence of latent vulnerability traits that underlie the emergence of depression and identify the association of low BDNF with normal corticosterone serum concentrations as a predictive biomarker of vulnerability to depression.