PDF(Pubmed)
Abstract：
Fetal hypoxia and maternal stress frequently culminate in neuropsychiatric afflictions in life. To replicate this condition, we employed a model of prenatal severe hypoxia (PSH) during days 14-16 of rat gestation. Subsequently, both control and PSH rats at 3 months old were subjected to episodes of inescapable stress to induce learned helplessness (LH). The results of the open field test revealed an inclination towards depressive-like behavior in PSH rats. Following LH episodes, control (but not PSH) rats displayed significant anxiety. LH induced an increase in glucocorticoid receptor (GR) levels in extrahypothalamic brain structures, with enhanced nuclear translocation in the hippocampus (HPC) observed both in control and PSH rats. However, only control rats showed an increase in GR nuclear translocation in the amygdala (AMG). The decreased GR levels in the HPC of PSH rats correlated with elevated levels of hypothalamic corticotropin-releasing hormone (CRH) compared with the controls. However, LH resulted in a reduction of the CRH levels in PSH rats, aligning them with those of control rats, without affecting the latter. This study presents evidence that PSH leads to depressive-like behavior in rats, associated with alterations in the glucocorticoid system. Notably, these impairments also contribute to increased resistance to severe stressors.
摘要：
胎儿缺氧和母体压力经常导致生活中的神经精神疾病。要复制这种情况，我们采用了大鼠妊娠14-16天产前严重缺氧（PSH）模型。随后，3个月大的对照和PSH大鼠都经历了不可避免的压力发作，以诱发学习无助（LH）。野外试验的结果表明，PSH大鼠倾向于抑郁样行为。LH发作后，对照组(而非PSH)大鼠表现出显著的焦虑。LH诱导下丘脑外脑结构中糖皮质激素受体（GR）水平的增加，在对照和PSH大鼠中观察到海马（HPC）的核易位增强。然而,只有对照大鼠显示杏仁核（AMG）中GR核易位增加。与对照组相比，PSH大鼠HPC中GR水平的降低与下丘脑促肾上腺皮质激素释放激素（CRH）水平的升高有关。然而,LH导致PSH大鼠的CRH水平降低，将它们与对照大鼠的对齐，而不影响后者。这项研究提供了PSH导致大鼠抑郁样行为的证据，与糖皮质激素系统的改变有关。值得注意的是,这些损伤也有助于增加对严重压力源的抵抗力。
