Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2024 Apr 20;131:110945. doi: 10.1016/j.pnpbp.2024.110945. Epub 2024 Jan 17.
Stressful events during pregnancy impact on the progeny neurodevelopment. However, little is known about preconceptional stress effects. The rat social isolation represents an animal model of chronic stress inducing a variety of dysfunctions. Moreover, social deprivation during adolescence interferes with key neurodevelopmental processes. Here, we investigated the development of behavioural, neurochemical and redox alterations in the male offspring of socially isolated female rats before pregnancy, reared in group (GRP) or in social isolation (ISO) from weaning until young-adulthood. To this aim, females were reared in GRP or in ISO conditions, from PND21 to PND70, when they were mated. Their male offspring was housed in GRP or ISO conditions through adolescence and until PND70, when passive avoidance-PA, novel object recognition-NOR and open field-OF tests were performed. Levels of noradrenaline (NA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), glutamate (GLU) and GABA were assessed in the prefrontal cortex (PFC). Moreover, cortical ROS levels were quantified, as well as NF-kB and the NADPH oxidase NOX2 expression, redox status (expressed as GSH:GSSG ratio) and SOD1 amount. A significant decrease of the latency time in the PA was observed in the offspring of ISO females. In the NOR test, while a significant increase in the exploratory activity towards the novel object was observed in the offspring of GRP females, no significant differences were found in the offspring of ISO females. No significant differences were found in the OF test among experimental groups. Theoffspring of ISO females showed increased NA and 5-HIAA levels, whereas in the offspring persistently housed in isolation condition from weaninguntil adulthood, we detected reduced 5-HT levels and ehnanced 5-HIAA amount. No significant changes in GLU concentrations were detected, while decreased GABA content was observed in the offspring of ISO females exposed to social isolation. Increased ROS levels as well as reduced NF-κB, NOX2 expression were detected in the offspring of ISO females. This was accompanied by reduced redox status and enhanced SOD1 levels. In conclusion, our results suggest that female exposure to chronic social stress before pregnancy might have a profound influence on the offspring neurodevelopment in terms of cognitive, neurochemical and redox-related alterations, identifying this specific time window for possible preventive and therapeutic strategies.
怀孕期间的应激事件会影响后代的神经发育。然而，关于孕前应激的影响知之甚少。大鼠社交隔离代表了一种诱导多种功能障碍的慢性应激动物模型。此外，青春期的社会剥夺会干扰关键的神经发育过程。在这里，我们研究了在怀孕前，雌性大鼠在社交隔离下（ISO）或群体饲养（GRP）下生长，其雄性后代的行为、神经化学和氧化还原变化的发展。为此，雌性大鼠从 PND21 到 PND70 在 GRP 或 ISO 条件下饲养，然后进行交配。它们的雄性后代在青春期和 PND70 之前一直被安置在 GRP 或 ISO 条件下，然后进行被动回避（PA）、新物体识别（NOR）和旷场（OF）测试。在额皮质（PFC）中评估去甲肾上腺素（NA）、血清素（5-HT）、5-羟吲哚乙酸（5-HIAA）、谷氨酸（GLU）和 GABA 的水平。此外，还量化了皮质 ROS 水平，以及 NF-kB 和 NADPH 氧化酶 NOX2 的表达、氧化还原状态（表示为 GSH：GSSG 比）和 SOD1 量。在 ISO 雌性后代的 PA 中观察到潜伏期显著缩短。在 NOR 测试中，GRP 雌性后代对新物体的探索性活动显著增加，而 ISO 雌性后代则没有显著差异。实验组之间 OF 测试无显著差异。ISO 雌性后代的 NA 和 5-HIAA 水平升高，而在持续从断奶到成年期隔离饲养的 ISO 后代中，我们发现 5-HT 水平降低，5-HIAA 量增加。GLU 浓度无显著变化，而 ISO 雌性后代的 GABA 含量降低。ISO 雌性后代的 ROS 水平升高，NF-κB 和 NOX2 的表达降低。这伴随着氧化还原状态的降低和 SOD1 水平的升高。总之，我们的结果表明，怀孕前母体暴露于慢性社会应激可能会对后代的神经发育产生深远的影响，包括认知、神经化学和氧化还原相关的改变，确定这个特定的时间窗口可能用于预防和治疗策略。
