Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Neurosci Biobehav Rev. 2022 Aug;139:104746. doi: 10.1016/j.neubiorev.2022.104746. Epub 2022 Jun 16.
Exposure to early life stress (ELS) may lead to long-lasting neurobiological and behavioral impairments. Alterations in the immune system and neuroinflammatory state induced by ELS exposure are considered risk factors for developing psychiatric disorders. Here, we performed a systematic review and meta-analysis of rodent studies investigating the short and long-term effects of ELS exposure on anti and pro-inflammatory cytokines in brain tissues. Our analysis shows that animals exposed to ELS present an increase in pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. On the other hand, no alteration was observed in the anti-inflammatory cytokine IL-10. Meta-regression revealed that alterations were more prominent in the hippocampus of adult animals that were exposed to more extended periods of ELS. These inflammatory effects were not permanent since few alterations were identified in aged animals. Our findings suggest that ELS exposure alters pro-inflammatory cytokines expression and may act as a primer for a secondary challenge that may induce lifelong immune alterations. Moreover, the actual evidence is insufficient to comprehend the relationship between anti-inflammatory cytokines and ELS fully.
早期生活应激(ELS)暴露可能导致持久的神经生物学和行为损伤。ELS 暴露引起的免疫系统和神经炎症状态的改变被认为是发展为精神障碍的风险因素。在这里,我们对研究 ELS 暴露对脑组织中抗炎和促炎细胞因子的短期和长期影响的啮齿动物研究进行了系统评价和荟萃分析。我们的分析表明,暴露于 ELS 的动物表现出促炎细胞因子 IL-1β、IL-6 和 TNF-α 的增加。另一方面,抗炎细胞因子 IL-10 没有观察到改变。元回归显示,在暴露于更长时间 ELS 的成年动物的海马体中,这些炎症变化更为明显。这些炎症效应不是永久性的,因为在老年动物中很少发现改变。我们的研究结果表明,ELS 暴露改变了促炎细胞因子的表达,可能作为引发终身免疫改变的二次挑战的诱因。此外,实际证据还不足以充分理解抗炎细胞因子与 ELS 之间的关系。