N-乙酰半胱氨酸能缓解青少年 EAAC1-/- 小鼠和早期生活压力模型大鼠的抑郁行为

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Sciences Pub Date : 2024-10-07 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.97723
Han-Byeol Kim, Yu-Jin Kim, Ye-Ji Lee, Ji-Young Yoo, Yoori Choi, Eun-Mee Kim, Sang Won Suh, Ran-Sook Woo
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引用次数: 0

摘要

早年的不良经历与青春期精神病理学风险的增加有关。在之前的一项研究中,我们证实了新生儿母体分离(NMS)与社会隔离会导致男性青少年出现冲动和抑郁样行为。此外,它还会显著降低兴奋性氨基酸载体 1(EAAC1)在海马中的表达。在此基础上,我们研究了谷胱甘肽的前体--N-乙酰半胱氨酸(NAC)对早期生活压力(ELS)模型大鼠和 EAAC1-/- 小鼠的影响。EAAC1 在向神经元转运谷氨酸和半胱氨酸方面发挥着双重作用。我们的研究结果表明,在 ELS 模型中,女性青少年也表现出与男性类似的行为缺陷。注射 NAC 可挽救男性和女性 NMS 模型中的抑郁样行为,但只改善了男性的冲动行为。此外,我们还观察到 NMS 模型大鼠腹侧海马(vHPC)和前额叶皮层中活性氧化应激(ROS)和神经炎症的增加,NAC 治疗可减轻这些症状。值得注意的是,NAC逆转了EAAC1在NMS模型大鼠vHPC中的表达减少。在EAAC1-/-小鼠中,明显存在严重的冲动和抑郁样行为,而NAC干预只改善了抑郁样行为。总之,我们的研究结果表明,ELS 是青春期抑郁和冲动行为的诱因。此外,EAAC1在神经元中的半胱氨酸摄取功能可能特别与抑郁而非冲动行为有关。
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N-Acetylcysteine Alleviates Depressive-Like Behaviors in Adolescent EAAC1-/- Mice and Early Life Stress Model Rats.

Exposure to adverse experiences during early life is associated with an increased risk of psychopathology during adolescence. In a previous study, we demonstrated that neonatal maternal separation (NMS) combined with social isolation led to impulsive and depressive-like behaviors in male adolescents. Additionally, it significantly reduced the expression of excitatory amino acid carrier 1 (EAAC1) in the hippocampus. Building upon this work, we investigated the effects of N-acetylcysteine (NAC), a precursor to glutathione, in early-life stress (ELS) model rats and in EAAC1-/- mice. EAAC1 plays a dual role in transporting both glutamate and cysteine into neurons. Our findings revealed that female adolescents subjected to in the ELS model also exhibited behavioral defects similar to those of males. NAC injection rescued depressive-like behaviors in both male and female NMS models, but it improved impulsive behavior only in males. Furthermore, we observed increased reactive oxidative stress (ROS) and neuroinflammation in the ventral hippocampus (vHPC) and prefrontal cortex of NMS model rats, which were mitigated by NAC treatment. Notably, NAC reversed the reduced expression of EAAC1 in the vHPC of NMS model rats. In EAAC1-/- mice, severe impulsive and depressive-like behaviors were evident, and the NAC intervention improved only depressive-like behaviors. Collectively, our results suggest that ELS contributes to depression and impulsive behaviors during adolescence. Moreover, the cysteine uptake function of EAAC1 in neurons may be specifically related to depression rather than impulsive behavior.

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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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