Institute of Medical Physiology "Richard Burian", School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Institute of Pathophysiology, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Biomed Res Int. 2019 Jun 10;2019:3426092. doi: 10.1155/2019/3426092. eCollection 2019.
Anxiety is one of the most frequent psychiatric disorders. Despite the fact that most studies describe an anxiolytic effect of testosterone, hyperandrogenemia in mothers is assumed to be related to an increased risk of mood disorders in their offspring. An increasing body of scientific evidence suggests that an altered expression of interneuronal markers of the hippocampus may be the cause of anxiety. The aim of this study was to examine the influence of maternal hyperandrogenemia on behavioral parameters of anxiety-like behavior, neuropeptide Y (NPY) and parvalbumin (PV) expression in the hippocampus, and the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex. Pregnant female Wistar albino rats were treated with testosterone undecanoate on the 20th day of gestation. Anxiety-like behavior in adult female offspring was evaluated by the elevated plus maze test and the open field. The number of PV and NPY immunoreactive cells in the hippocampus was determined immunohistochemically. The level of BDNF expression in the hippocampus and cerebral cortex was analyzed with the Western blot test. Prenatal hyperandrogenization increased anxiety-like behavior in female offspring and decreased expression of NPY+ and PV+ in the CA1 region of the hippocampus as compared to the control group. BDNF expression in the hippocampus and cerebral cortex of prenatally androgenized female offspring was significantly increased in comparison with the controls. Prenatal hyperandrogenization may be the cause of anxiety-like behavior in female offspring. Decrease in NPY and PV expression in the hippocampus may explain the possible mechanism of hyperandrogenization induced anxiety.
焦虑症是最常见的精神障碍之一。尽管大多数研究都描述了睾酮的抗焦虑作用，但母亲的高雄激素血症被认为与后代情绪障碍的风险增加有关。越来越多的科学证据表明，海马体内神经内分沁标志物的表达改变可能是焦虑的原因。本研究旨在探讨母体高雄激素血症对焦虑样行为的行为参数、海马神经肽 Y（NPY）和钙结合蛋白（PV）表达以及海马和大脑皮层脑源性神经营养因子（BDNF）水平的影响。妊娠第 20 天，Wistar 白化雌性大鼠用十一酸睾酮处理。通过高架十字迷宫试验和旷场试验评估成年雌性后代的焦虑样行为。通过免疫组织化学方法确定海马体中 PV 和 NPY 免疫反应性细胞的数量。用 Western blot 试验分析海马和大脑皮层中 BDNF 的表达水平。与对照组相比，产前雄激素化增加了雌性后代的焦虑样行为，并降低了海马 CA1 区的 NPY+和 PV+表达。与对照组相比，产前雄激素化雌性后代海马和大脑皮层中的 BDNF 表达显著增加。产前高雄激素血症可能是雌性后代出现焦虑样行为的原因。海马体中 NPY 和 PV 表达的减少可能解释了高雄激素血症诱导焦虑的可能机制。
