Traffic-related particulate matter affects behavior, inflammation, and neural integrity in a developmental rodent model.
Traffic-related particulate matter affects behavior, inflammation, and neural integrity in a developmental rodent model.
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DOI：
10.1016/j.envres.2020.109242
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发表时间：
2020-02
影响因子：
8.3
通讯作者：
B. Nephew;A. Németh;N. Hudda;G. Beamer;P. Mann;J. Petitto;R. Cali;M. Febo;P. Kulkarni;G. Poirier;J. King;J. Durant;D. Brugge
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文献类型：
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作者：
B. Nephew;A. Németh;N. Hudda;G. Beamer;P. Mann;J. Petitto;R. Cali;M. Febo;P. Kulkarni;G. Poirier;J. King;J. Durant;D. Brugge
最近的研究表明，接触空气中的颗粒物 (PM) 与认知迟缓、抑郁、焦虑、自闭症和神经退行性疾病有关；然而，PM 在这些结果的病因学中的作用尚不清楚。因此，需要进行对照动物研究，以更好地阐明 PM 影响这些健康结果的原因和机制。我们评估了妊娠期和生命早期接触交通相关颗粒物对幼年雄性大鼠的社交和焦虑相关行为、认知、炎症标志物和神经完整性的影响。妊娠期和哺乳期大鼠暴露于来自波士顿（美国马萨诸塞州）交通隧道的 PM，每周 5 天，每天 5 小时，持续 6 周（妊娠 3 周，哺乳期 3 周）。雾化 PM 的细小部分（以 PM2.5 测量）的目标暴露浓度为 200 µg/m3。为了评估焦虑和认知功能，F1 雄性幼年在 32-60 天龄时接受了高架平台、蟋蟀捕食、筑巢、社交行为和大理石埋藏测试。行为测试完成后，对这些动物的多种细胞因子和生长因子进行了测量，并用扩散张量 MRI 分析了它们的大脑，以评估神经完整性。 PM 暴露对产仔数、体重或后代生长没有影响；然而，在发育过程中暴露于 PM 的 F1 窝幼仔表现出显着增加的焦虑 (p= 0.04)、认知能力下降（反映在较差的巢穴组织中）(p= 0.04)，以及社交游戏和异体梳理的减少 (p= 0.003)。对离体大脑的 MRI 分析显示，暴露于 PM 的 F1 幼鱼的前扣带回和海马神经组织的结构完整性降低（分别为 p < 0.01，p = 0.03）。暴露于 PM 的 F1 幼年雄性也表现出 IL-18 (p = 0.03) 和 VEGF (p = 0.04) 血浆水平显着降低，并且这些变化与焦虑相关行为呈负相关。母鼠及其后代在妊娠和哺乳期间长期接触与交通相关的颗粒物，会降低社会行为，增加焦虑，损害认知，降低炎症和生长因子水平（与行为变化相关），并破坏幼年雄性后代的神经完整性。我们的研究结果进一步证明，妊娠期和哺乳期接触与交通相关的空气污染与自闭症谱系障碍和其他疾病（包括社交和认知缺陷和/或焦虑增加）的病因有关。
Recent studies indicate that exposure to airborne particulate matter (PM) is associated with cognitive delay, depression, anxiety, autism, and neurodegenerative diseases; however, the role of PM in the etiology of these outcomes is not well-understood. Therefore, there is a need for controlled animal studies to better elucidate the causes and mechanisms by which PM impacts these health outcomes. We assessed the effects of gestational and early life exposure to traffic-related PM on social- and anxiety-related behaviors, cognition, inflammatory markers, and neural integrity in juvenile male rats. Gestating and lactating rats were exposed to PM from a Boston (MA, USA) traffic tunnel for 5 h/day, 5 days/week for 6 weeks (3 weeks gestation, 3 weeks lactation). The target exposure concentration for the fine fraction of nebulized PM, measured as PM2.5, was 200 μg/m3. To assess anxiety and cognitive function, F1 male juveniles underwent elevated platform, cricket predation, nest building, social behavior and marble burying tests at 32–60 days of age. Upon completion of behavioral testing, multiple cytokines and growth factors were measured in these animals and their brains were analyzed with diffusion tensor MRI to assess neural integrity. PM exposure had no effect on litter size or weight, or offspring growth; however, F1 litters developmentally exposed to PM exhibited significantly increased anxiety (p= 0.04), decreased cognition reflected in poorer nest-organization (p= 0.04), and decreased social play and allogrooming (p= 0.003). MRI analysis ofex vivobrains revealed decreased structural integrity of neural tissues in the anterior cingulate and hippocampus in F1 juveniles exposed to PM (p < 0.01, p = 0.03, respectively). F1 juvenile males exposed to PM also exhibited significantly decreased plasma levels of both IL-18 (p = 0.03) and VEGF (p = 0.04), and these changes were inversely correlated with anxiety-related behavior. Chronic exposure of rat dams and their offspring to traffic-related PM during gestation and lactation decreases social behavior, increases anxiety, impairs cognition, decreases levels of inflammatory and growth factors (which are correlated with behavioral changes), and disrupts neural integrity in the juvenile male offspring. Our findings add evidence that exposure to traffic-related air pollution during gestation and lactation is involved in the etiology of autism spectrum disorder and other disorders which include social and cognitive deficits and/or increased anxiety.