Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt, Suite No. 100, Seattle, WA, 98105, USA.
Center on Human Development and Disability, University of Washington, Seattle, WA, USA.
Arch Toxicol. 2018 May;92(5):1815-1829. doi: 10.1007/s00204-018-2180-5. Epub 2018 Mar 10.
Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit adult neurogenesis in mice. Mice were exposed for 6 h to DE at a PM concentration of 250-300 μg/m, followed by assessment of adult neurogenesis in the hippocampal subgranular zone (SGZ), the subventricular zone (SVZ), and olfactory bulb (OB). DE impaired cellular proliferation in the SGZ and SVZ in males, but not females. DE reduced adult neurogenesis, with male mice showing fewer new neurons in the SGZ, SVZ, and OB, and females showing fewer new neurons only in the OB. To assess whether blocking microglial activation protected against DE-induced suppression of adult hippocampal neurogenesis, male mice were pre-treated with pioglitazone (PGZ) prior to DE exposure. The effects of DE exposure on microglia, as well as neuroinflammation and oxidative stress, were reduced by PGZ. PGZ also antagonized DE-induced suppression of neurogenesis in the SGZ. These results suggest that DE exposure impairs adult neurogenesis in a sex-dependent manner, by a mechanism likely to involve microglia activation and neuroinflammation.
成人神经发生是指神经干细胞在成年大脑特定区域产生新的功能性神经元的过程，这一过程贯穿人的一生。值得注意的是，神经退行性疾病和精神疾病表现出神经发生抑制、小胶质细胞激活和神经炎症。交通相关的空气污染已被证明对中枢神经系统有不良影响。由于空气污染暴露的主要影响是小胶质细胞激活，以及随之而来的氧化应激和神经炎症，我们研究了急性暴露于柴油废气（DE）是否会抑制小鼠的成年神经发生。小鼠在 PM 浓度为 250-300μg/m 的 DE 中暴露 6 小时，然后评估海马颗粒下区（SGZ）、脑室下区（SVZ）和嗅球（OB）中的成年神经发生。DE 损害了雄性小鼠的 SGZ 和 SVZ 中的细胞增殖，但对雌性小鼠没有影响。DE 减少了成年神经发生，雄性小鼠的 SGZ、SVZ 和 OB 中新神经元较少，而雌性小鼠仅在 OB 中新神经元较少。为了评估阻断小胶质细胞激活是否能防止 DE 诱导的成年海马神经发生抑制，雄性小鼠在 DE 暴露前用吡格列酮（PGZ）进行预处理。PGZ 还降低了 DE 暴露对小胶质细胞以及神经炎症和氧化应激的影响。PGZ 还拮抗了 DE 对 SGZ 中神经发生的抑制作用。这些结果表明，DE 暴露以一种可能涉及小胶质细胞激活和神经炎症的机制，以性别依赖的方式损害成年神经发生。
