Data corresponding to the publication by Di Miceli, Rossitto, Martinat, Marchaland, Kharbouche, Graland, Younes, Séré, Aubert, Rabbaa Khabbaz, Madore, Delpech, Martín & Layé.

Title of the study: Modified neuroimmune processes and emotional behaviour in weaned and late adolescent male and female mice born via caesarean section.Authors: Mathieu Di Miceli, Moïra Rossitto, Maud Martinat, Flore Marchaland, Sarah Kharbouche, Marion Graland, Farah Younes, Alexandra Séré, Agnès Aubert, Lydia Rabbaa Khabbaz, Charlotte Madore, Jean-Christophe Delpech, Rebeca Martín and Sophie Layé.Publication: <i>Scientific Report</i>, 2024.Abstract:Elective and emergency Caesarean section (C-section) procedures are on the rise, exceeding the recommended guidelines by the World Health Organization. Higher morbidities and long-term health conditions are correlated to C-section deliveries, including neurodevelopmental disorders. During C-section delivery, newborns are not exposed to the vaginal commensal flora, which impedes the early establishment of the gut microbiota. The latter is essential for adequate neuro-immune processes to take place during infancy. In this study, we used a validated model of mice born by C-section (CSD), which mimics clinical observations of dysregulated gut microbiota. Animals were either born naturally or by CSD, before being adopted by dams who underwent delivery within the 12 preceding hours. Behavioural analyses were conducted at post-natal day (PND) 21 and 55. Our results indicate that animals born by C-section present significantly higher body weight in late (PND40-P53) but not early adolescence (PND21-P27), compared to animals born by vaginal delivery (VD). Male animals delivered by C-section presented significantly lower exploration time of the novel arm in the Y Maze test at PND55. However, at PND21, abnormal social interaction was witnessed in male and female animals born by CSD, with significantly decreased time spent interacting during the social interaction test. At both PND21 and PND55, animals from both sexes born by C-section presented significantly decreased time spent in the open arm of the Elevated Plus Maze test, compared to control animals. We then measured the expression of genes associated to neuroimmune interactions (microglia phenotype), inflammatory mediators and lipids in several brain structures of VD and CSD mice at PND21 and PND55. At weaning, animals born by CSD presented altered microglia, inflammatory and lipid metabolism signatures, with increased expression of Cd36, Csf1r and Tnfα in different brain regions of males, but not in females. At PND64, Csf1r, Tmem119 as well as C3ar1 were significantly increased in males born by C-section, but not in females. In males born by vaginal delivery, the expression of Cd36 at PND64 was correlated to anxiety at PND55, whilst a correlation between the expression of Clec7a and the number of head dippings in the elevated plus maze was also noted in males born by CSD. Altogether, our study shows altered emotional behaviour in animals delivered by CSD, which is likely explained by underlying neuro-inflammatory processes in different brain regions. Our work further supports the long-term consequences of CSD on brain health.FigShare identifier: 10.6084/m9.figshare.25459183

研究标题：剖宫产出生的断奶期及青春晚期雌雄小鼠的神经免疫过程与情绪行为改变。
作者：Mathieu Di Miceli、Moïra Rossitto、Maud Martinat、Flore Marchaland、Sarah Kharbouche、Marion Graland、Farah Younes、Alexandra Séré、Agnès Aubert、Lydia Rabbaa Khabbaz、Charlotte Madore、Jean-Christophe Delpech、Rebeca Martín 及 Sophie Layé。
发表期刊：《科学报告（Scientific Report）》，2024年。
摘要：择期与急诊剖宫产（Caesarean Section, C-section）手术量呈上升趋势，已超出世界卫生组织（World Health Organization, WHO）推荐的操作规范。剖宫产分娩与更高的发病率及长期健康问题相关，其中包括神经发育障碍。剖宫产分娩时，新生儿不会接触阴道共生菌群，这会阻碍肠道菌群（gut microbiota）的早期定植；而肠道菌群对于婴儿期正常神经免疫过程的开展至关重要。本研究采用经验证的剖宫产小鼠模型（Caesarean Section Delivery, CSD），该模型可模拟肠道菌群失调的临床现象。实验小鼠分为自然分娩组与剖宫产组，所有幼崽均由分娩时间在12小时内的代母母鼠哺育。分别于出生后天数（post-natal day，PND）21与55时开展行为学分析。结果显示，与阴道分娩（vaginal delivery, VD）组小鼠相比，剖宫产组小鼠在青春晚期（PND40~PND53）的体重显著更高，但在青春早期（PND21~PND27）无此差异。PND55时，剖宫产组雄性小鼠在Y迷宫实验（Y Maze test）中对新臂的探索时长显著更短。但在PND21时，剖宫产组雌雄小鼠均表现出异常社交行为，其在社交互动实验（social interaction test）中的互动时长显著降低。在PND21与PND55两个时间点，剖宫产组雌雄小鼠在高架十字迷宫实验（Elevated Plus Maze test）中进入开放臂的时长均显著低于对照组小鼠。随后，我们分别在PND21与PND55时，检测了阴道分娩组与剖宫产组小鼠多个脑区中与神经免疫互作（小胶质细胞表型，microglia phenotype）、炎症介质（inflammatory mediators）及脂质相关的基因表达水平。断奶期时，剖宫产组小鼠的小胶质细胞、炎症及脂质代谢特征发生改变：雄性小鼠不同脑区中Cd36、Csf1r与Tnfα的表达水平升高，但雌性小鼠无此变化。PND64时，剖宫产组雄性小鼠体内Csf1r、Tmem119及C3ar1的表达水平显著升高，雌性小鼠则无此现象。在阴道分娩组雄性小鼠中，PND64时Cd36的表达水平与PND55时的焦虑水平呈正相关；而在剖宫产组雄性小鼠中，Clec7a的表达水平与高架十字迷宫实验中的探头次数呈显著相关。综上，本研究证实剖宫产分娩小鼠存在情绪行为异常，该现象或由不同脑区潜在的神经炎症过程所介导；本研究进一步佐证了剖宫产分娩对大脑健康的长期影响。
FigShare 标识符：10.6084/m9.figshare.25459183