产前和产后对受孕前应激小鼠模型行为发育的影响

IF 4.3 2区 医学 Q1 NEUROSCIENCES Neurobiology of Stress Pub Date : 2024-02-03 DOI:10.1016/j.ynstr.2024.100614
Joseph Scarborough , Monica Iachizzi , Sina M. Schalbetter , Flavia S. Müller , Ulrike Weber-Stadlbauer , Juliet Richetto
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引用次数: 0

摘要

孕期抑郁症不利于孕妇的健康,并可能对后代的发育和心理健康造成长期影响。在这种情况下,妊娠环境和产后环境都可能受到抑郁病理的负面影响。然而,评估产前和产后抑郁暴露的贡献是不同的、交互的还是累积的,是一项挑战,因为目前还不清楚产前影响是由于对胎儿发育的直接影响,还是因为产前症状在产后仍在继续。临床前模型试图回答这个问题,方法是在母体妊娠期间施加能诱发类似抑郁状态的压力,并研究其对后代的影响。我们本研究的目的是在一种基于社会隔离饲养(SIR)的新型孕前压力模型中,将子宫内的直接压力与母体行为的可能变化区分开来。通过在该模型中使用交叉寄养范式,我们发现虽然社会隔离饲养会导致母体行为的微妙变化,但在后代身上观察到的行为变化是由性别、产前和产后母体因素之间复杂的相互作用所驱动的。事实上,雄性后代对产前环境更敏感,其行为和转录变化由生母驱动,而雌性后代则可能受到产前和产后环境之间更复杂的相互作用的影响,代养母亲的重要影响也说明了这一点。总之,我们的研究结果表明,男性和女性的后代易受孕前母体压力影响的时间窗口和行为领域不同,因此在研究介导暴露于这种压力的负面影响的机制时,将两性都包括在内非常重要。
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Prenatal and postnatal influences on behavioral development in a mouse model of preconceptional stress

Depression during pregnancy is detrimental for the wellbeing of the expectant mother and can exert long-term consequences on the offspring's development and mental health. In this context, both the gestational environment and the postpartum milieu may be negatively affected by the depressive pathology. It is, however, challenging to assess whether the contributions of prenatal and postnatal depression exposure are distinct, interactive, or cumulative, as it is unclear whether antenatal effects are due to direct effects on fetal development or because antenatal symptoms continue postnatally. Preclinical models have sought to answer this question by implementing stressors that induce a depressive-like state in the dams during pregnancy and studying the effects on the offspring. The aim of our present study was to disentangle the contribution of direct stress in utero from possible changes in maternal behavior in a novel model of preconceptional stress based on social isolation rearing (SIR). Using a cross-fostering paradigm in this model, we show that while SIR leads to subtle changes in maternal behavior, the behavioral changes observed in the offspring are driven by a complex interaction between sex, and prenatal and postnatal maternal factors. Indeed, male offspring are more sensitive to the prenatal environment, as demonstrated by behavioral and transcriptional changes driven by their birth mother, while females are likely affected by more complex interactions between the pre and the postpartum milieu, as suggested by the important impact of their surrogate foster mother. Taken together, our findings suggest that male and female offspring have different time-windows and behavioral domains of susceptibility to maternal preconceptional stress, and thus underscore the importance of including both sexes when investigating the mechanisms that mediate the negative consequences of exposure to such stressor.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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