Schulz Kalynn M, Pearson Jennifer N, Gasparrini Mary E, Brooks Kayla F, Drake-Frazier Chakeer, Zajkowski Megan E, Kreisler Alison D, Adams Catherine E, Leonard Sherry, Stevens Karen E
Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Building 500, 1300 East 17th Place, Aurora, CO 80045, USA.
Neuroscience Program, University of Colorado Anschutz Medical Campus, RC-1, MS 8351, Rm 7107 12800 E. 19th Ave, Aurora, CO 80045, USA.
Behav Brain Res. 2014 Jul 15;268:104-10. doi: 10.1016/j.bbr.2014.03.031. Epub 2014 Mar 24.
Brain cholinergic dysfunction is associated with neuropsychiatric illnesses such as depression, anxiety, and schizophrenia. Maternal stress exposure is associated with these same illnesses in adult offspring, yet the relationship between prenatal stress and brain cholinergic function is largely unexplored. Thus, using a rodent model, the current study implemented an intervention aimed at buffering the potential effects of prenatal stress on the developing brain cholinergic system. Specifically, control and stressed dams were fed choline-supplemented or control chow during pregnancy and lactation, and the anxiety-related behaviors of adult offspring were assessed in the open field, elevated zero maze and social interaction tests. In the open field test, choline supplementation significantly increased center investigation in both stressed and nonstressed female offspring, suggesting that choline-supplementation decreases female anxiety-related behavior irrespective of prenatal stress exposure. In the elevated zero maze, prenatal stress increased anxiety-related behaviors of female offspring fed a control diet (normal choline levels). However, prenatal stress failed to increase anxiety-related behaviors in female offspring receiving supplemental choline during gestation and lactation, suggesting that dietary choline supplementation ameliorated the effects of prenatal stress on anxiety-related behaviors. For male rats, neither prenatal stress nor diet impacted anxiety-related behaviors in the open field or elevated zero maze. In contrast, perinatal choline supplementation mitigated prenatal stress-induced social behavioral deficits in males, whereas neither prenatal stress nor choline supplementation influenced female social behaviors. Taken together, these data suggest that perinatal choline supplementation ameliorates the sex-specific effects of prenatal stress.
脑胆碱能功能障碍与抑郁症、焦虑症和精神分裂症等神经精神疾病有关。母体应激暴露与成年后代的这些相同疾病有关，但产前应激与脑胆碱能功能之间的关系在很大程度上尚未得到探索。因此，本研究使用啮齿动物模型实施了一项干预措施，旨在缓冲产前应激对发育中的脑胆碱能系统的潜在影响。具体而言，在怀孕和哺乳期给对照母鼠和应激母鼠喂食补充胆碱的饲料或对照饲料，并在旷场试验、高架零迷宫试验和社交互动试验中评估成年后代的焦虑相关行为。在旷场试验中，补充胆碱显著增加了应激和非应激雌性后代的中央探索行为，这表明补充胆碱可降低雌性的焦虑相关行为，而与产前应激暴露无关。在高架零迷宫试验中，产前应激增加了喂食对照饲料（正常胆碱水平）的雌性后代的焦虑相关行为。然而，产前应激未能增加在妊娠和哺乳期接受补充胆碱的雌性后代的焦虑相关行为，这表明饮食中补充胆碱可改善产前应激对焦虑相关行为的影响。对于雄性大鼠，产前应激和饮食均未影响旷场试验或高架零迷宫试验中的焦虑相关行为。相反，围产期补充胆碱减轻了产前应激诱导的雄性社交行为缺陷，而产前应激和胆碱补充均未影响雌性社交行为。综上所述，这些数据表明围产期补充胆碱可改善产前应激的性别特异性影响。
