Emotional dysregulation following prenatal stress is associated with altered prefrontal cortex responsiveness to an acute challenge in adolescence

IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY
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Abstract

Exposure to prenatal stress (PNS) has the potential to elicit multiple neurobiological alterations and increase the susceptibility to psychiatric disorders. Moreover, gestational stress may sensitize the brain toward an altered response to subsequent challenges. Here, we investigated the effects of PNS in rats and assessed whether these animals exhibit an altered brain responsiveness to an acute stress (AS) during adolescence. From gestational day 14 until delivery, Sprague Dawley dams were exposed to PNS or left undisturbed. During adolescence (PND38 to PND41), offspring were tested in the social interaction and splash test. At PND44 half of the animals were exposed to 5 min of forced swim stress. Males and Females exposed to PNS showed reduced sociability and increased anhedonic-like behavior. At the molecular level, exposure of adolescent rats to AS produced increased activation of the amygdala and ventral and dorsal hippocampus. Regarding the prefrontal cortex (PFC), we observed a pronounced activation in PNS males exposed to AS. Cell-type specific transcriptional analyses revealed a significant imbalance in the activation of PFC excitatory and inhibitory neurons in PNS males and females exposed to AS. Furthermore, stressed males exhibited disrupted HPA-axis function, while females showed impairments in the modulation of antioxidant genes. Our study shows that PNS induces emotional dysregulation and alters the responsiveness of the PFC to an acute stressor. Moreover, the disruption of excitatory and inhibitory balance during adolescence could influence the ability to respond to challenging events that may contribute to precipitate a full-blown pathologic condition.
产前应激后的情绪失调与青春期前额叶皮层对急性挑战的反应能力改变有关。
产前应激(PNS)可能会引起多种神经生物学改变,并增加精神疾病的易感性。此外,妊娠应激还可能使大脑对后续挑战的反应发生改变。在此,我们研究了PNS对大鼠的影响,并评估了这些动物在青春期是否表现出对急性应激(AS)的大脑反应性改变。从妊娠第 14 天开始到分娩,Sprague Dawley 大鼠的母鼠会暴露于 PNS 或不受干扰。在青春期(PND38至PND41),对后代进行社交互动和飞溅试验。在 PND44 时,一半的动物暴露于 5 分钟的强迫游泳应激。暴露于 PNS 的雄性和雌性动物表现出交际能力下降和类似厌食症的行为增加。在分子水平上,将青春期大鼠暴露于 AS 会导致杏仁核、腹侧和背侧海马的激活增加。在前额叶皮层(PFC)方面,我们观察到暴露于强直性脊柱炎的雄性前额叶皮层明显活化。细胞类型特异性转录分析表明,在暴露于 AS 的 PNS 雄性和雌性中,PFC 兴奋性和抑制性神经元的激活明显失衡。此外,受压男性表现出 HPA 轴功能紊乱,而女性则表现出抗氧化基因调节功能受损。我们的研究表明,PNS 会诱发情绪失调,并改变前脑功能区对急性应激源的反应能力。此外,青春期兴奋和抑制平衡的破坏可能会影响对挑战性事件的反应能力,从而导致全面病变。
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来源期刊
CiteScore
12.00
自引率
1.80%
发文量
153
审稿时长
56 days
期刊介绍: Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.
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