Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy.
Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
Psychoneuroendocrinology. 2021 Feb;124:104794. doi: 10.1016/j.psyneuen.2020.104794. Epub 2020 Jul 6.
Early life stress, especially when experienced during the first period of life, affects the brain developmental trajectories leading to an enhanced vulnerability for stress-related psychiatric disorders later in life. Although both clinical and preclinical studies clearly support this association, the biological pathways deregulated by such exposure, and the effects in shaping the neurodevelopmental trajectories, have so far been poorly investigated. By using the prenatal stress (PNS) model, a well-established rat model of early life stress, we performed transcriptomic analyses in the prefrontal cortex of rats exposed or not to PNS and sacrificed at different postnatal days (PNDs 21, 40, 62). We first investigated the long-lasting mechanisms and pathways affected in the PFC. We have decided to focus on the prefrontal cortex because we have previously shown that this brain region is highly sensitive to PNS exposure. We found that adult animals exposed to PNS show alterations in 389 genes, mainly involved in stress and inflammatory signalling. We then wanted to establish whether PNS exposure could also affect the neurodevelopmental trajectories in order to identify the most critical temporal window. We found that PNS rats show the most significant changes during adolescence (between PND 40 versus PND 21), with alterations of several pathways related to stress, inflammation and metabolism, which were maintained until adulthood.
早期生活压力，特别是在生命早期经历的压力，会影响大脑的发育轨迹，导致日后更容易患上与压力相关的精神疾病。尽管临床和临床前研究都清楚地支持这种关联，但到目前为止，这种暴露所导致的生物学途径失调，以及对神经发育轨迹的影响，还没有得到充分的研究。我们使用产前应激（PNS）模型，这是一种成熟的大鼠早期生活压力模型，对暴露于或未暴露于 PNS 的大鼠的前额叶皮层进行了转录组分析，并在不同的出生后天数（PND21、40、62）处死。我们首先研究了 PFC 中受长期影响的机制和途径。我们之所以选择前额叶皮层作为研究对象，是因为我们之前已经证明了这个脑区对 PNS 暴露非常敏感。我们发现，暴露于 PNS 的成年动物有 389 个基因发生了改变，这些基因主要涉及应激和炎症信号转导。然后，我们想确定 PNS 暴露是否也会影响神经发育轨迹，以确定最关键的时间窗口。我们发现，PNS 大鼠在青春期（PND40 与 PND21 之间）表现出最显著的变化，与应激、炎症和代谢相关的几个途径发生了改变，这些改变一直持续到成年。
