Han-Byeol Kim, Yu-Jin Kim, Ye-Ji Lee, Ji-Young Yoo, Yoori Choi, Eun-Mee Kim, Sang Won Suh, Ran-Sook Woo
{"title":"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","authors":"Han-Byeol Kim, Yu-Jin Kim, Ye-Ji Lee, Ji-Young Yoo, Yoori Choi, Eun-Mee Kim, Sang Won Suh, Ran-Sook Woo","doi":"10.7150/ijbs.97723","DOIUrl":null,"url":null,"abstract":"<p><p>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<sup>-/-</sup> 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<sup>-/-</sup> 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.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 14","pages":"5450-5473"},"PeriodicalIF":8.2000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528454/pdf/","citationCount":"0","resultStr":"{\"title\":\"N-Acetylcysteine Alleviates Depressive-Like Behaviors in Adolescent EAAC1<sup>-/-</sup> Mice and Early Life Stress Model Rats.\",\"authors\":\"Han-Byeol Kim, Yu-Jin Kim, Ye-Ji Lee, Ji-Young Yoo, Yoori Choi, Eun-Mee Kim, Sang Won Suh, Ran-Sook Woo\",\"doi\":\"10.7150/ijbs.97723\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sup>-/-</sup> 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<sup>-/-</sup> 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. 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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.
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.