Sex-specific peripheral and central responses to stress-induced depression and treatment in a mouse model.,Journal of Neuroscience Research

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Sex-specific peripheral and central responses to stress-induced depression and treatment in a mouse model.
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2020-09-11 , DOI: 10.1002/jnr.24724
Kristina K Deonaraine ₁ , Qian Wang _{2,

3,

4} , Haoxiang Cheng ₂ , Kenny L Chan ₁ , Hsiao-Yun Lin ₁ , Kalena Liu ₅ , Lyonna F Parise ₁ , Flurin Cathomas ₁ , Katherine B Leclair ₁ , Meghan E Flanigan ₁ , Long Li ₁ , Hossein Aleyasin ₁ , Christopher Guevara ₁ , Ke Hao ₂ , Bin Zhang _{2,

3,

4} , Scott J Russo ₁ , Jun Wang _{5,

6}

Affiliation

Major depressive disorder affects ~20% of the world population and is characterized by strong sexual dimorphism with females being two to three times more likely to develop this disorder. Previously, we demonstrated that a combination therapy with dihydrocaffeic acid and malvidin‐glucoside to synergistically target peripheral inflammation and stress‐induced synaptic maladaptation in the brain was effective in alleviating chronic social defeat stress (CSDS)‐induced depression‐like phenotype in male mice. Here, we test the combination therapy in a female CSDS model for depression and compared sex‐specific responses to stress in the periphery and the central nervous system. Similar to male mice, the combination treatment is also effective in promoting resilience against the CSDS‐induced depression‐like behavior in female mice. However, there are sex‐specific differences in peripheral immune responses and differential gene regulation in the prefrontal cortex to chronic stress and to the treatment. These data indicate that while therapeutic approaches to combat stress‐related disorders may be effective in both sexes, the mechanisms underlying these effects differ, emphasizing the need for inclusion of both sexes in preclinical studies using animal models.

中文翻译：

小鼠模型中对应激诱导的抑郁和治疗的性别特异性外周和中枢反应。

重度抑郁症影响约 20% 的世界人口，其特征是强烈的性别二态性，女性患这种疾病的可能性是其他人的两到三倍。此前，我们证明，二氢咖啡酸和锦葵素-葡萄糖苷联合治疗可协同靶向外周炎症和应激诱导的大脑突触适应不良，可有效缓解雄性小鼠慢性社交失败压力 (CSDS) 诱导的抑郁样表型。在这里，我们在女性 CSDS 抑郁症模型中测试了联合疗法，并比较了外周和中枢神经系统对压力的性别特异性反应。与雄性小鼠类似，联合治疗也能有效提高雌性小鼠对 CSDS 诱导的抑郁样行为的恢复能力。然而，外周免疫反应和前额叶皮层对慢性压力和治疗的差异基因调控存在性别特异性差异。这些数据表明，虽然对抗压力相关疾病的治疗方法可能对两性都有效，但这些影响背后的机制不同，强调需要将两性纳入使用动物模型的临床前研究。

更新日期：2020-10-19

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