Mundorf Annakarina, Freund Nadja
Division of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr University Bochum, 44801 Bochum, Germany.
Institute for Systems Medicine and Department of Human Medicine, MSH Medical School, 20457 Hamburg, Germany.
Biomolecules. 2024 Dec 12;14(12):1587. doi: 10.3390/biom14121587.
Exposure to stress during early and late childhood can lead to long-lasting neurobiological and behavioral impairments. Although sensitive periods for stress exposure are well established, less is known about the trajectory of induced alterations throughout development. In this study, we investigated the impact of maternal separation (MS), social isolation, and their combination on anxiety-like behavior and gene expression across developmental stages. Sprague Dawley rats were exposed to one or both stressors and later assessed for anxiety-like behavior in juvenility, adolescence, and adulthood. mRNA levels of , a gene linked to early-life stress and depression, were measured in the medial prefrontal cortex to assess developmental changes. The results showed that MS had age- and sex-dependent effects on anxiety-like behavior. Juveniles exhibited less anxiety after MS, while adolescents showed more pronounced behavioral changes following social isolation. No behavioral changes were observed in adults. Males exhibited greater anxiety-like behavior than females in adolescence and adulthood, but not in juvenility. Female adults exposed to both MS and social isolation had significantly lower expression compared to controls. These findings highlight the dynamic effects of early stress across the lifespan, underscoring the critical role of adolescence and differential stress susceptibility by age and sex.
童年早期和晚期暴露于压力之下会导致长期的神经生物学和行为损伤。尽管压力暴露的敏感期已得到充分证实，但对于整个发育过程中诱发改变的轨迹了解较少。在本研究中，我们调查了母婴分离（MS）、社会隔离及其组合对不同发育阶段焦虑样行为和基因表达的影响。将斯普拉格-道利大鼠暴露于一种或两种应激源下，随后在幼年、青少年和成年期评估其焦虑样行为。在内侧前额叶皮质测量与早期生活压力和抑郁相关的基因的mRNA水平，以评估发育变化。结果表明，母婴分离对焦虑样行为具有年龄和性别依赖性影响。幼年大鼠在母婴分离后表现出较少的焦虑，而青少年大鼠在社会隔离后表现出更明显的行为变化。成年大鼠未观察到行为变化。在青少年期和成年期，雄性大鼠比雌性大鼠表现出更强烈的焦虑样行为，但在幼年期并非如此。与对照组相比，同时暴露于母婴分离和社会隔离的成年雌性大鼠的 表达显著降低。这些发现突出了早期压力在整个生命周期中的动态影响，强调了青春期的关键作用以及年龄和性别导致的不同压力易感性。
