Background and Hypothesis Redox dysregulation has been proposed as a convergent point of childhood trauma and the emergence of psychiatric disorders, such as schizophrenia (SCZ). A critical region particularly vulnerable to environmental insults during adolescence is the ventral hippocampus (vHip). However, the impact of severe stress on vHip redox states and their functional consequences, including behavioral and electrophysiological changes related to SCZ, are not entirely understood. Study Design After exposing adolescent animals to physical stress (postnatal day, PND31–40), we explored social and cognitive behaviors (PND47–49), the basal activity of pyramidal glutamate neurons, the number of parvalbumin (PV) interneurons, and the transcriptomic signature of the vHip (PND51). We also evaluated the impact of stress on the redox system, including mitochondrial respiratory function, reactive oxygen species (ROS) production, and glutathione (GSH) levels in the vHip and serum. Study Results Adolescent-stressed animals exhibited loss of sociability, cognitive impairment, and vHip excitatory/inhibitory (E/I) imbalance. Genome-wide transcriptional profiling unveiled the impact of stress on redox system- and synaptic-related genes. Stress impacted mitochondrial respiratory function and changes in ROS levels in the vHip. GSH and glutathione disulfide (GSSG) levels were elevated in the serum of stressed animals, while GSSG was also increased in the vHip and negatively correlated with sociability. Additionally, PV interneuron deficits in the vHip caused by adolescent stress were associated with oxidative stress. Conclusions Our results highlight the negative impact of adolescent stress on vHip redox regulation and mitochondrial function, which are partially associated with E/I imbalance and behavioral abnormalities related to SCZ.

中文翻译：

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青少年压力引起的腹侧海马氧化还原失调是与精神分裂症相关的行为缺陷和兴奋/抑制失衡的基础

背景和假设氧化还原失调已被认为是儿童创伤和精神疾病（例如精神分裂症（SCZ））出现的交汇点。青春期特别容易受到环境侵害的关键区域是腹侧海马体（vHip）。然而，严重压力对 vHip 氧化还原状态的影响及其功能后果，包括与 SCZ 相关的行为和电生理变化，尚不完全清楚。研究设计将青春期动物暴露于身体压力后（出生后一天，PND31-40），我们探索了社会和认知行为（PND47-49）、锥体谷氨酸神经元的基础活动、小白蛋白（PV）中间神经元的数量以及转录组学vHip (PND51) 的签名。我们还评估了应激对氧化还原系统的影响，包括线粒体呼吸功能、活性氧 (ROS) 产生以及 vHip 和血清中的谷胱甘肽 (GSH) 水平。研究结果 青春期压力动物表现出社交能力丧失、认知障碍和 vHip 兴奋/抑制 (E/I) 失衡。全基因组转录谱揭示了压力对氧化还原系统和突触相关基因的影响。压力影响线粒体呼吸功能和 vHip 中 ROS 水平的变化。应激动物血清中的谷胱甘肽和二硫化谷胱甘肽 (GSSG) 水平升高，而 vHip 中的 GSSG 也升高，并且与社交能力呈负相关。此外，青少年压力引起的 vHip 中 PV 中间神经元缺陷与氧化应激有关。结论 我们的结果强调了青少年压力对 vHip 氧化还原调节和线粒体功能的负面影响，这部分与 E/I 失衡和 SCZ 相关的行为异常有关。