Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Neuroscience. 2011 May 19;182:43-61. doi: 10.1016/j.neuroscience.2011.03.008. Epub 2011 Mar 29.
Early life stressors have life-long functional and anatomical consequences. Though many neurotransmitters are involved in the functional impact of early life stress, dopamine seems to be important because of its roles in motor control, adaptation to stressful conditions, mood, cognition, attention and reward. Thus, in the present study, we investigated the way that early life stress, in the form of maternal separation (MS), affects the populations of tyrosine hydroxylase-immunoreactive (TH-IR) dopaminergic neurons in rat midbrain structures during ontogenesis. We included in the study the sub-regions of the substantia nigra (SN) and the ventral tegmental area (VTA). In both the control and MS rats, we found that the estimated total number of TH-expressing neurons fluctuated during ontogenesis. Moreover, MS influenced the number of TH-IR cells, especially in the SN pars reticulata (SNr) and VTA. Shortly after the termination of MS, on postnatal day (PND) 15, a decrease in the estimated total number of TH-IR neurons was observed in the SNr and VTA (in both males and females). On PND 35, MS caused a transient increase in the number of TH-IR cells only in the SNr of female rats. On PND 70, MS affected the number of TH-IR neurons in the VTA of females; specifically, an increase in the number of these cells was observed. Additionally, MS did not alter TH-IR cell sizes or the total levels of TH (measured by Western blot analysis) in the SN and VTA for all stages of ontogenesis in both males and females. The results from the study herein indicate that early life stress has enduring effects on the populations of midbrain TH-expressing dopaminergic neurons (especially in female rats), which are critically important for dopamine-regulated brain function throughout ontogenesis.
早期生活压力源会产生终身的功能和解剖后果。虽然许多神经递质参与了早期生活压力的功能影响，但多巴胺似乎很重要，因为它在运动控制、适应应激条件、情绪、认知、注意力和奖励方面发挥作用。因此，在本研究中，我们研究了早期生活压力（以母婴分离的形式）对发育过程中大鼠中脑结构中酪氨酸羟化酶免疫反应性（TH-IR）多巴胺能神经元群体的影响。我们将研究包括黑质（SN）和腹侧被盖区（VTA）的亚区。在对照组和 MS 组大鼠中，我们发现 TH 表达神经元的估计总数在发育过程中波动。此外，MS 影响了 TH-IR 细胞的数量，尤其是在 SN 网状部（SNr）和 VTA。在 MS 结束后不久，即生后第 15 天（PND），我们观察到 SNr 和 VTA 中估计的 TH-IR 神经元总数减少（雄性和雌性大鼠均如此）。在 PND35 时，MS 仅在雌性大鼠的 SNr 中引起 TH-IR 细胞数量的短暂增加。在 PND70 时，MS 影响了雌性大鼠 VTA 中 TH-IR 神经元的数量；具体而言，观察到这些细胞数量增加。此外，MS 没有改变 SN 和 VTA 中所有发育阶段雄性和雌性大鼠 TH-IR 细胞大小或 TH 的总水平（通过 Western blot 分析测量）。本研究的结果表明，早期生活压力对中脑表达 TH 的多巴胺能神经元群体（尤其是雌性大鼠）具有持久影响，这对多巴胺调节的大脑功能在整个发育过程中至关重要。
