San Felipe Diego, Martín-Sánchez Beatriz, Zekri-Nechar Khaoula, Moya Marta, Llorente Ricardo, Zamorano-León Jose J, Marco Eva M, López-Gallardo Meritxell
Department of Physiology, School of Medicine, Complutense University of Madrid, Pza. Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain.
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Department of Public Health and Maternal-Child Health, School of Medicine, Complutense University of Madrid, Pza. Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain.
Biology (Basel). 2024 Dec 4;13(12):1011. doi: 10.3390/biology13121011.
Early life stress (ELS) is associated with an increased risk for neuropsychiatric disorders, and both neuroinflammation and mitochondrial dysfunction seem to be central to mental health. Herein, using an animal model of ELS, a single episode of maternal deprivation (MD, 24 h on pnd 9) extensively documented to elicit behavioural anomalies in male and female Wistar rats, we investigated its consequences in terms of neuroinflammation and mitochondrial dynamics in the prefrontal cortex (PFC) and the hippocampal formation (HCF). MD differentially affected the brain content of cytokines: MD induced a transient increase in pro-inflammatory cytokines (IL-1β and IL-6) in the PFC, as well as in the levels of the anti-inflammatory cytokine IL-10 in the HCF. MD also induced a significant decrease mitochondria citrate synthase activity, but MD did not exert significant changes in mitochondria Complex IV activity, revealing a generalized decrease in mitochondrial density without any change in mitochondrial respiration. In the present study, we demonstrate that MD induces neuroinflammatory processes in specific brain regions. Additional research is needed to better understand the temporal pattern of such changes, their impact on the developing brain, and their participation in the already well-known behavioural consequences of MD.
早期生活应激(ELS)与神经精神疾病风险增加相关,神经炎症和线粒体功能障碍似乎都是心理健康的核心因素。在此,我们使用一种ELS动物模型,即单次母婴分离(MD,出生后第9天24小时),这种模型已被广泛记录可引发雄性和雌性Wistar大鼠的行为异常。我们研究了其在前额叶皮质(PFC)和海马结构(HCF)中对神经炎症和线粒体动力学的影响。MD对细胞因子的脑内含量有不同影响:MD诱导PFC中促炎细胞因子(IL-1β和IL-6)短暂增加,以及HCF中抗炎细胞因子IL-10水平升高。MD还导致线粒体柠檬酸合酶活性显著降低,但MD并未使线粒体复合物IV活性发生显著变化,这表明线粒体密度普遍降低,而线粒体呼吸无任何改变。在本研究中,我们证明MD在特定脑区诱导神经炎症过程。需要进一步研究以更好地理解这些变化的时间模式、它们对发育中大脑的影响以及它们在MD已知行为后果中的作用。