Neigh Gretchen N, Nemeth Christina L, Kelly Sean D, Hardy Emily E, Bourke Chase, Stowe Zachary N, Owens Michael J
Department of Psychiatry and Behavioral Sci., Emory University, Atlanta, GA, USA; Department of Physiology, Emory University, Atlanta, GA, USA.
Department of Physiology, Emory University, Atlanta, GA, USA.
Physiol Behav. 2017 Apr 1;172:24-30. doi: 10.1016/j.physbeh.2016.07.009. Epub 2016 Jul 13.
Prenatal stress has been linked to deficits in neurological function including deficient social behavior, alterations in learning and memory, impaired stress regulation, and susceptibility to adult disease. In addition, prenatal environment is known to alter cardiovascular health; however, limited information is available regarding the cerebrovascular consequences of prenatal stress exposure. Vascular disturbances late in life may lead to cerebral hypoperfusion which is linked to a variety of neurodegenerative and psychiatric diseases. The known impact of cerebrovascular compromise on neuronal function and behavior highlights the importance of characterizing the impact of stress on not just neurons and glia, but also cerebrovasculature. Von Willebrand factor has previously been shown to be impacted by prenatal stress and is predictive of cerebrovascular health. Here we assess the impact of prenatal stress on von Willebrand factor and related angiogenic factors. Furthermore, we assess the potential protective effects of concurrent anti-depressant treatment during in utero stress exposure on the assessed cerebrovascular endpoints. Prenatal stress augmented expression of von Willebrand factor which was prevented by concurrent in utero escitalopram treatment. The functional implications of this increase in von Willebrand factor remain elusive, but the presented data demonstrate that although prenatal stress did not independently impact total vascularization, exposure to chronic stress in adulthood decreased blood vessel length. In addition, the current study demonstrates that production of reactive oxygen species in the hippocampus is decreased by prenatal exposure to escitalopram. Collectively, these findings demonstrate that the prenatal experience can cause complex changes in adult cerebral vascular structure and function.
产前应激与神经功能缺陷有关,包括社交行为缺陷、学习和记忆改变、应激调节受损以及易患成人疾病。此外,已知产前环境会改变心血管健康;然而,关于产前应激暴露对脑血管的影响,目前可用信息有限。晚年的血管紊乱可能导致脑灌注不足,这与多种神经退行性疾病和精神疾病有关。脑血管损伤对神经元功能和行为的已知影响凸显了不仅要研究应激对神经元和神经胶质细胞的影响,还要研究其对脑血管系统影响的重要性。此前已有研究表明,血管性血友病因子会受到产前应激的影响,并且可预测脑血管健康。在此,我们评估产前应激对血管性血友病因子及相关血管生成因子的影响。此外,我们评估了在子宫内应激暴露期间同时进行抗抑郁治疗对所评估的脑血管终点的潜在保护作用。产前应激会增加血管性血友病因子的表达,而在子宫内同时使用艾司西酞普兰治疗可预防这种增加。血管性血友病因子增加的功能意义尚不清楚,但现有数据表明,尽管产前应激并未独立影响总血管生成,但成年期暴露于慢性应激会减少血管长度。此外,当前研究表明,产前暴露于艾司西酞普兰可降低海马体中活性氧的产生。总体而言,这些发现表明产前经历可导致成人大脑的血管结构和功能发生复杂变化。