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首页> 外文期刊>BMC Neuroscience >Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes
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Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes

机译：怀孕前的社交挫败压力导致成年男性后代产生抑郁样行为和认知缺陷：与神经生物学变化的相关性

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Epidemiological surveys and studies with animal models have established a relationship between maternal stress and affective disorders in their offspring. However, whether maternal depression before pregnancy influences behaviour and related neurobiological mechanisms in the offspring has not been studied. A social defeat stress (SDS) maternal rat model was established using the resident-intruder paradigm with female specific pathogen-free Wistar rats and evaluated with behavioural tests. SDS maternal rats showed a significant reduction in sucrose preference and locomotor and exploratory activities after 4?weeks of stress. In the third week of the experiment, a reduction in body weight gain was observed in SDS animals. Sucrose preference, open field, the elevated-plus maze, light–dark box, object recognition, the Morris water maze, and forced swimming tests were performed using the 2-month-old male offspring of the female SDS rats. Offspring subjected to pre-gestational SDS displayed enhanced anxiety-like behaviours, reduced exploratory behaviours, reduced sucrose preference, and atypical despair behaviours. With regard to cognition, the offspring showed significant impairments in the retention phase of the object recognition test, but no effect was observed in the acquisition phase. These animals also showed impairments in recognition memory, as the discrimination index in the Morris water maze test in this group was significantly lower for both 1?h and 24?h memory retention compared to controls. Corticosterone, adrenocorticotropic hormone, and monoamine neurotransmitters levels were determined using enzyme immunoassays or radioimmunoassays in plasma, hypothalamus, left hippocampus, and left prefrontal cortex samples from the offspring of the SDS rats. These markers of hypothalamic–pituitary–adrenal axis responsiveness and the monoaminergic system were significantly altered in pre-gestationally stressed offspring. Brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and serotonin transporter (SERT) protein levels were evaluated using western blotting with right hippocampus and right prefrontal cortex samples. Expression levels of BDNF, pCREB, and SERT in the offspring were also altered in the hippocampus and in the prefrontal cortex; however, there was no effect on CREB. We conclude that SDS before pregnancy might induce depressive-like behaviours, cognitive deficits, and neurobiological alterations in the offspring.
机译：流行病学调查和动物模型研究已经建立了孕产妇压力与后代情感障碍之间的关系。但是，尚未研究孕前母亲抑郁是否会影响其后代的行为和相关的神经生物学机制。使用具有雌性特定病原体的Wistar大鼠的常驻入侵者模式建立了社会挫败应激（SDS）母鼠模型，并通过行为测试对其进行了评估。在应激4周后，SDS母鼠的蔗糖偏爱，运动和探索活动显着降低。在实验的第三周，在SDS动物中观察到体重增加减少。使用雌性SDS大鼠的两个月大的雄性后代进行了蔗糖偏爱，开放视野，高架迷宫，明暗框，物体识别，莫里斯水迷宫和强迫游泳测试。接受妊娠前SDS的后代表现出增强的焦虑样行为，减少的探索行为，减少的蔗糖偏爱和非典型的绝望行为。关于认知，后代在对象识别测试的保留阶段显示出明显的损伤，但在获得阶段未观察到影响。这些动物也表现出识别记忆障碍，因为与对照组相比，该组Morris水迷宫测试中的1？h和24？h记忆保持力的辨别指数均显着降低。使用酶免疫法或放射免疫法测定SDS大鼠后代血浆，下丘脑，左海马和左前额叶皮层样品中的皮质酮，促肾上腺皮质激素和单胺类神经递质的水平。在妊娠前应激的后代中，这些下丘脑-垂体-肾上腺轴反应性和单胺能系统的标志物发生了显着改变。使用western blotting对右侧海马和右侧前额叶皮层样品评估了脑源性神经营养因子（BDNF），环状腺苷单磷酸反应元件结合蛋白（CREB），磷酸化CREB（pCREB）和5-羟色胺转运蛋白（SERT）的蛋白水平。海马和前额叶皮层中BDNF，pCREB和SERT的表达水平也发生了改变。但是，对CREB没有影响。我们得出的结论是，怀孕前的SDS可能会引起后代的抑郁样行为，认知缺陷和神经生物学改变。

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