Department of Psychology, Sacred Heart University, Fairfield, CT 06825, United States of America.
Department of Psychology, Sacred Heart University, Fairfield, CT 06825, United States of America.
Horm Behav. 2019 Jan;107:26-34. doi: 10.1016/j.yhbeh.2018.11.004. Epub 2018 Nov 26.
The endocrine disruptor, Bisphenol-A (BPA), alters many behavioral and neural parameters in rodents. BPA administration to gonadally intact adolescent rats increases anxiety, impairs spatial memory, and decreases dendritic spine density when measured in adulthood. Since BPA's action seems to be mediated through gonadal steroid receptors, the current experiments were done in ovariectomized (OVX) female rats to examine the effects on behavior and spine density of adolescent BPA exposure under controlled hormone conditions. OVX (postnatal day, PND, 21) female Sprague-Dawley rats (n = 66) received subcutaneous injections of BPA (40 μg/kg/bodyweight), 17β-Estradiol (E2, 50 μg/kg/bodyweight), or saline during adolescence (PND 38-49). Following the last injection brains were processed for Golgi impregnation (Exp1), behavioral and spine density in adolescence (Exp2), or in adulthood (Exp3). In Exp1, E2 increased spine density in CA1 pyramidal cells and BPA decreased spine density in granule cells of the dentate gyrus (DG). In Exp2, BPA impaired spatial memory on the object placement (OP) task, E2 increased spine density in CA1, BPA decreased spine density in the DG and the medial prefrontal cortex (mPFC). When measured in adulthood (Exp3), BPA impaired OP and object recognition (OR) performance, E2 increased spine density in CA1, and BPA decreased spine density in CA1, the mPFC and the DG. Results provide novel data on the effects of adolescent BPA in an OVX model and are compared to data in intact animals and within the context of understanding the importance of the profound neuronal alterations occurring during adolescent development.
内分泌干扰物双酚 A（BPA）会改变啮齿动物的许多行为和神经参数。在青春期给性腺完整的雄性大鼠注射 BPA 会增加焦虑，损害空间记忆，并在成年时降低树突棘密度。由于 BPA 的作用似乎是通过性腺类固醇受体介导的，因此目前的实验是在去卵巢（OVX）雌性大鼠中进行的，以检查在受控激素条件下青春期 BPA 暴露对行为和树突棘密度的影响。OVX（出生后第 21 天）雌性 Sprague-Dawley 大鼠（n=66）在青春期（第 38-49 天）接受 BPA（40μg/kg/体重）、17β-雌二醇（E2，50μg/kg/体重）或生理盐水的皮下注射。最后一次注射后，大脑进行高尔基浸渍处理（实验 1）、青春期的行为和树突棘密度（实验 2）或成年期的行为和树突棘密度（实验 3）。在实验 1 中，E2 增加 CA1 锥体神经元的树突棘密度，BPA 减少齿状回（DG）颗粒细胞的树突棘密度。在实验 2 中，BPA 损害了物体放置（OP）任务的空间记忆，E2 增加了 CA1 中的树突棘密度，BPA 减少了 DG 和内侧前额叶皮层（mPFC）中的树突棘密度。在成年期测量时（实验 3），BPA 损害了 OP 和物体识别（OR）表现，E2 增加了 CA1 中的树突棘密度，BPA 减少了 CA1、mPFC 和 DG 中的树突棘密度。这些结果提供了青春期 BPA 在 OVX 模型中的影响的新数据，并与完整动物的数据进行了比较，并在理解青春期发育过程中发生的深刻神经元改变的重要性的背景下进行了比较。
