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聚肌胞苷酸诱导的母体免疫激活导致雄性大鼠后代的自我梳理行为增加:与母鼠产后异常静止哺乳有关。

Poly(I:C)-induced maternal immune activation causes elevated self-grooming in male rat offspring: Involvement of abnormal postpartum static nursing in dam.

作者信息

Lan Xing-Yu, Gu You-Yu, Li Ming-Juan, Song Tian-Jia, Zhai Fu-Jun, Zhang Yong, Zhan Jiang-Shan, Böckers Tobias M, Yue Xiao-Nan, Wang Jia-Nan, Yuan Shuo, Jin Meng-Ying, Xie Yu-Fei, Dang Wan-Wen, Hong Hai-Heng, Guo Zi-Rui, Wang Xue-Wei, Zhang Rong

机构信息

Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.

Neuroscience Research Institute, Peking University, Beijing, China.

出版信息

Front Cell Dev Biol. 2023 Mar 16;11:1054381. doi: 10.3389/fcell.2023.1054381. eCollection 2023.

Abstract

Maternal immune activation (MIA) is closely related to the onset of autism-like behaviors in offspring, but the mechanism remains unclear. Maternal behaviors can influence offspring's development and behaviors, as indicated in both human and animal studies. We hypothesized that abnormal maternal behaviors in MIA dams might be other factors leading to delayed development and abnormal behaviors in offspring. To verify our hypothesis, we analyzed poly(I:C)-induced MIA dam's postpartum maternal behavior and serum levels of several hormones related to maternal behavior. Pup's developmental milestones and early social communication were recorded and evaluated in infancy. Other behavioral tests, including three-chamber test, self-grooming test, open field test, novel object recognition test, rotarod test and maximum grip test, were performed in adolescence of pups. Our results showed that MIA dams exhibit abnormal static nursing behavior but normal basic care and dynamic nursing behavior. The serum levels of testosterone and arginine vasopressin in MIA dams were significantly reduced compared with control dams. The developmental milestones, including pinna detachment, incisor eruption and eye opening, were significantly delayed in MIA offspring compared with control offspring, while the weight and early social communication showed no significant differences between the two groups. Behavioral tests performed in adolescence showed that only male MIA offspring display elevated self-grooming behaviors and reduced maximum grip. In conclusion, MIA dams display abnormal postpartum static nursing behavior concomitantly with reduced serum levels of testosterone and arginine vasopressin, possibly involving in the pathogenesis of delayed development and elevated self-grooming in male offspring. These findings hint that improving dam's postpartum maternal behavior might be a potential regime to counteract delayed development and elevated self-grooming in male MIA offspring.

摘要

母体免疫激活(MIA)与后代自闭症样行为的发生密切相关,但其机制仍不清楚。正如人类和动物研究所示,母体行为会影响后代的发育和行为。我们假设,MIA 母鼠的异常母体行为可能是导致后代发育延迟和行为异常的其他因素。为了验证我们的假设,我们分析了聚肌胞苷酸(poly(I:C))诱导的 MIA 母鼠的产后母体行为以及几种与母体行为相关的激素的血清水平。在幼年期记录并评估幼崽的发育里程碑和早期社交交流情况。在幼崽青春期进行了其他行为测试,包括三室测试、自我梳理测试、旷场测试、新物体识别测试、转棒测试和最大抓握力测试。我们的结果表明,MIA 母鼠表现出异常的静态哺乳行为,但基本护理和动态哺乳行为正常。与对照母鼠相比,MIA 母鼠血清中的睾酮和精氨酸加压素水平显著降低。与对照后代相比,MIA 后代的发育里程碑,包括耳廓分离、门齿萌出和睁眼,明显延迟,而两组之间的体重和早期社交交流没有显著差异。在青春期进行的行为测试表明,只有雄性 MIA 后代表现出自我梳理行为增加和最大抓握力降低。总之,MIA 母鼠表现出产后异常的静态哺乳行为,同时血清睾酮和精氨酸加压素水平降低,这可能与雄性后代发育延迟和自我梳理行为增加的发病机制有关。这些发现提示,改善母鼠的产后母体行为可能是对抗雄性 MIA 后代发育延迟和自我梳理行为增加的一种潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c597/10062710/ab8a15d08210/fcell-11-1054381-g001.jpg

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