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早期生活压力重塑雄性和雌性幼年大鼠的应激应对能力。

Early-Life Stress Reprograms Stress-Coping Abilities in Male and Female Juvenile Rats.

机构信息

Laboratorio de Neuroprogramación Perinatal del Neurodesarrollo, Instituto de Biología Celular Y Neurociencias "Prof. Eduardo De Robertis" (IBCN)- Facultad de Medicina, Universidad de Buenos Aires, 2155 Paraguay St. CABA, C1121ABG, Buenos Aires, Argentina.

Instituto de Investigaciones Biotecnológicas (IIB), Universidad Nacional de San Martín, Buenos Aires, Argentina.

出版信息

Mol Neurobiol. 2021 Nov;58(11):5837-5856. doi: 10.1007/s12035-021-02527-2. Epub 2021 Aug 19.

Abstract

Prenatal stress (PS) is a major risk factor for the development of emotional disorders in adulthood that may be mediated by an altered hypothalamic-pituitary-adrenal axis response to stress. Although the early onset of stress-related disorders is recognized as a major public health problem, to date, there are relatively few studies that have examined the incidence of early-life stressors in younger individuals. In this study, we assessed PS impact on the stress-coping response of juvenile offspring in behavioral tests and in the induced molecular changes in the hippocampus. Furthermore, we assessed if pregnancy stress could be driving changes in patterns of maternal behavior during early lactation. We found that PS modified stress-coping abilities of both sex offspring. In the hippocampus, PS increased the expression of bdnf-IV and crfr1 and induced sex difference changes on glucocorticoids and BDNF mRNA receptor levels. PS changed the hippocampal epigenetic landscape mainly in male offspring. Stress during pregnancy enhanced pup-directed behavior of stressed dams. Our study indicates that exposure to PS, in addition to enhanced maternal behavior, induces dynamic neurobehavioral variations at juvenile ages of the offspring that should be considered adaptive or maladaptive, depending on the characteristics of the confronting environment. Our present results highlight the importance to further explore risk factors that appear early in life that will be important to allow timely prevention strategies to later vulnerability to stress-related disorders.

摘要

产前应激(PS)是成年后发生情绪障碍的一个主要危险因素,其发生机制可能与下丘脑-垂体-肾上腺轴对应激的反应改变有关。尽管应激相关障碍的早期发病已被认为是一个主要的公共卫生问题,但迄今为止,相对较少的研究检查了生命早期应激源在年轻个体中的发生率。在这项研究中,我们评估了 PS 对幼年后代应激应对反应的影响,通过行为测试和海马诱导的分子变化进行评估。此外,我们还评估了妊娠应激是否会导致哺乳期早期母性行为模式的改变。我们发现 PS 改变了雌雄后代的应激应对能力。在海马中,PS 增加了 bdnf-IV 和 crfr1 的表达,并诱导了糖皮质激素和 BDNF mRNA 受体水平的性别差异变化。PS 改变了海马的表观遗传景观,主要是在雄性后代中。孕期应激增强了应激母鼠对幼崽的定向行为。我们的研究表明,除了增强母性行为外,PS 暴露还会导致后代在青少年时期产生动态的神经行为变化,这些变化应被视为适应性的或不适应性的,具体取决于所面临环境的特征。我们目前的结果强调了进一步探索生命早期出现的风险因素的重要性,这些因素对于及时采取预防策略以防止以后出现与应激相关的障碍至关重要。

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