Worcester Polytechnic Institute, Department of Biology and Biotechnology, 100 Institute Rd, Worcester, MA, 01609, USA; University of Massachusetts Medical School, Department of Psychiatry, 55 N. Lake Road, Worcester, MA, 01655, USA.
Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA, 01536, USA.
Environ Res. 2020 Apr;183:109242. doi: 10.1016/j.envres.2020.109242. Epub 2020 Feb 17.
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/m. 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 of ex vivo brains 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.
最近的研究表明，空气中的颗粒物（PM）暴露与认知延迟、抑郁、焦虑、自闭症和神经退行性疾病有关；然而，PM 对这些结果的病因的作用还没有被很好地理解。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 PM 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。妊娠和哺乳期大鼠每天暴露于来自波士顿（马萨诸塞州，美国）交通隧道的 PM 5 小时，每周 5 天，共 6 周（妊娠 3 周，哺乳期 3 周）。雾化 PM 的细颗粒（以 PM2.5 计）的目标暴露浓度为 200μg/m。为了评估焦虑和认知功能，F1 雄性幼鼠在 32-60 天大时接受高架平台、蟋蟀捕食、筑巢、社交行为和大理石掩埋测试。在完成行为测试后，对这些动物进行了多种细胞因子和生长因子的测量，并对其大脑进行了扩散张量 MRI 分析，以评估神经完整性。PM 暴露对产仔数或体重或后代生长没有影响；然而，在 PM 下发育暴露的 F1 后代表现出明显增加的焦虑（p=0.04），反映在较差的巢组织（p=0.04）和社交玩耍和异体梳理（p=0.003）认知下降。对离体大脑的 MRI 分析显示，在暴露于 PM 的 F1 幼鼠的前扣带回和海马体中的神经组织的结构完整性降低（p<0.01，p=0.03）。暴露于 PM 的 F1 幼鼠的血浆中白细胞介素 18（p=0.03）和血管内皮生长因子（p=0.04）的水平也显著降低，这些变化与焦虑相关的行为呈负相关。在妊娠和哺乳期，母体大鼠及其后代慢性接触交通相关 PM 会降低社交行为，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，在妊娠和哺乳期暴露于交通相关的空气污染与自闭症谱系障碍和其他包括社交和认知缺陷以及/或增加焦虑的疾病的病因有关。
