Data Sheet 1_Critical period plasticity is associated with resilience to short unpredictable stress.docx

Low resilience to stressful events can increase the risk of anxiety and depression. Resilience decreases with age, parallel to drastic changes in the quality of brain plasticity from juvenile to old age, suggesting that the type of plasticity found in the maturing brain promotes resilience. To indirectly test this, we administered short unpredictable stress to adult male and female wild type (WT) C57BL/6 mice, as well as to two groups of mice characterized by heightened cortical plasticity: adolescent C57BL/6 WT mice and adult mice that lack SynCAM 1 (Synaptic Cell Adhesion Molecule 1), a critical plasticity brake in the mature brain. We found that short unpredictable stress robustly increased core body temperature in all groups of mice, indicative of stress-induced hyperthermia (SIH) and confirming the efficacy of the stress paradigm. However, depressive-like behavior as measured though tail suspension test was increased in adult WT mice only, supporting that the type of plasticity found in the immature brains of adolescent WT and adult SynCAM 1 knockout (KO) mice promotes resilience to stress. All three groups of mice showed a mild increase in locomotor activity after stress, suggesting that the quality of plasticity does not correlate with resilience to anxiety-like phenotypes. Our study hence provides indirect evidence for the protective role of developmental plasticity during stress and points to new mechanisms that promote resilience to stress-induced depression.

个体对应激事件的抗压韧性低下会增加焦虑与抑郁的发病风险。抗压韧性随年龄增长而下降，这与大脑可塑性质量从幼年到老年的剧烈变化同步发生，提示成熟大脑中存在的可塑性类型可促进抗压韧性。为间接验证这一假说，我们对成年雄性和雌性野生型（wild type, WT）C57BL/6小鼠，以及两组皮层可塑性增强的小鼠施加了短期不可预测应激：青春期C57BL/6野生型小鼠，以及缺失突触细胞黏附分子1（Synaptic Cell Adhesion Molecule 1, SynCAM 1）的成年小鼠——该分子是成熟大脑中关键的可塑性抑制因子。本研究发现，短期不可预测应激可显著升高所有组小鼠的核心体温，该现象符合应激诱导性体温过高（stress-induced hyperthermia, SIH）的特征，证实了本次应激范式的有效性。然而，通过悬尾实验（tail suspension test）检测到的抑郁样行为仅在成年野生型小鼠中有所增加，这支持了青春期野生型小鼠未成熟大脑以及成年突触细胞黏附分子1基因敲除（knockout, KO）小鼠体内的可塑性类型可促进抗压韧性这一观点。三组小鼠在应激后均表现出运动活性的轻度升高，这提示可塑性质量与焦虑样表型的抗压韧性并无关联。因此，本研究为发育可塑性在应激过程中的保护作用提供了间接证据，并指明了可提升对应激诱导性抑郁抵抗能力的新机制。