Data_Sheet_1_Early Life Exposure to Tumor Necrosis Factor Induces Precocious Sensorimotor Reflexes Acquisition and Increases Locomotor Activity During Mouse Postnatal Development.xlsx

Inflammation appears as a cardinal mediator of the deleterious effect of early life stress exposure on neurodevelopment. More generally, immune activation during the perinatal period, and most importantly elevations of pro-inflammatory cytokines levels could contribute to psychopathology and neurological deficits later in life. Cytokines are also required for normal brain function in homeostatic conditions and play a role in neurodevelopmental processes. Despite these latter studies, whether pro-inflammatory cytokines such as Tumor Necrosis Factor (TNF) impact neurodevelopmental trajectories and behavior during the immediate postnatal period remains to be elucidated. To address this issue, we have injected mouse pups daily with recombinant TNF from postnatal day (P)1 to P5. This yielded a robust increase in peripheral and central TNF at P5, and also an increase of additional pro-inflammatory cytokines. Compared to control pups injected with saline, mice injected with TNF acquired the righting and the acoustic startle reflexes more rapidly and exhibited increased locomotor activity 2 weeks after birth. Our results extend previous work restricted to adult behaviors and support the notion that cytokines, and notably TNF, modulate early neurodevelopmental trajectories.

炎症是早期生命应激暴露对神经发育产生有害影响的核心介导因子。更广泛而言，围产期免疫激活，尤其是促炎细胞因子（pro-inflammatory cytokines）水平升高，可能会在日后引发精神病理症状与神经功能缺损。细胞因子亦是稳态条件下维持正常脑功能的必需物质，并参与神经发育过程。尽管已有上述相关研究，但诸如肿瘤坏死因子（Tumor Necrosis Factor, TNF）这类促炎细胞因子是否会在出生后早期影响神经发育轨迹与行为，仍有待阐明。为解决这一问题，本研究于出生后第1天至第5天（P1至P5）每日对幼鼠注射重组TNF。该处理使P5时外周与中枢的TNF水平显著升高，同时也使其他促炎细胞因子水平上升。与注射生理盐水的对照组幼鼠相比，注射TNF的幼鼠在出生2周后更快获得翻正反射与听觉惊反射，并表现出更高的运动活性。本研究结果拓展了此前仅针对成年行为的相关研究，并支持细胞因子（尤其是TNF）可调控早期神经发育轨迹这一观点。