Little is known regarding the adverse effects of chronic particulate matter (PM) inhalation on the central nervous system (CNS). The present study aimed to examine how PM exposure impacts on oxidative stress and inflammatory processes, as well as the expression of interneurons and perineuronal nets (PNNs) in the CNS. BALB/c mice (6-week-old females, n = 32) were exposed to 1 to 5 μm size diesel-extracted particles (DEPs) (100 μg/m³, 5 d/week, 5 h/day) and categorized into the following four groups: 1) 4-week DEP (n = 8); 2) 4-week control (n = 8), 3) 8-week DEP (n = 8); and 4) 8-week control (n = 8). The olfactory bulb, prefrontal cortex, temporal cortex, striatum, and cerebellum were harvested from the animals in each group. The expression of antioxidants (heme oxygenase 1 [HO-1] and superoxide dismutase 2 [SOD-2]), and markers of the unfolded protein response (X-box binding protein [XBP]-1S), inflammation (tumor necrosis factor-alpha [TNF-α]), and proliferation (neurotrophin-3 and brain-derived neurotrophic factor [BDNF]) were measured using reverse transcription polymerase chain reaction (PCR) and Western blotting. The expression levels of HO-1, SOD-2, XBP-1S, TNF-α, neurotrophin-3, and BDNF were compared among groups using the Mann–Whitney U test. The temporal cortex was immunostained for parvalbumin (PV) and Wisteria floribunda agglutinin (WFA). The numbers of PV- and WFA-positive cells were counted using a confocal microscope and analyzed with the Mann–Whitney U test. HO-1 expression was elevated in the prefrontal cortex, temporal cortex, striatum, and cerebellum of mice in the 8-week DEP group compared with the control group. Expression of SOD-2 and XBP-1S was elevated in the prefrontal cortex and striatum of the 8-week DEP group compared with the control group. TNF-α expression was elevated in the prefrontal cortex, temporal cortex, striatum, and cerebellum in the 4- and 8-week DEP groups compared with the control group. Neurotrophin-3 expression was decreased in the olfactory bulb and striatum of the 8-week DEP group compared with the control group. WFA density was increased in the 8-week DEP group compared with the control group. The PV and PV + WFA densities were decreased in the 4-week DEP group compared with the control group. Chronic DEP inhalation activated oxidative stress and inflammation in multiple brain regions. Chronic DEP inhalation increased PNNs and decreased the number of interneurons, which may contribute to PM exposure-related CNS dysfunction.

关于吸入慢性颗粒物（PM）对中枢神经系统（CNS）的不利影响知之甚少。本研究旨在检查PM暴露如何影响氧化应激和炎症过程，以及中枢神经系统中神经元和神经周围神经网（PNNs）的表达。BALB / c小鼠（6周龄雌性，n = 32）暴露于1至5μm大小的柴油提取颗粒（DEPs）（100μg/ m ³，5天/周，5小时/天），分为以下四组：1）4周DEP（n = 8）；2）4周控制（n = 8），3）8周DEP（n = 8）；和4）8周控制（n = 8）。从每组动物中收集嗅球，前额叶皮层，颞叶皮层，纹状体和小脑。抗氧化剂（血红素加氧酶1 [HO-1]和超氧化物歧化酶2 [SOD-2]）的表达，以及未折叠蛋白应答（X-box结合蛋白[XBP] -1S），炎症（肿瘤坏死因子-使用逆转录聚合酶链反应（PCR）和Western印迹法检测α（TNF-α）和增殖（神经营养蛋白3和脑源性神经营养因子[BDNF]）的表达。使用Mann-Whitney U比较各组中HO-1，SOD-2，XBP-1S，TNF-α，neurotrophin-3和BDNF的表达水平测试。对颞皮质进行了小白蛋白（PV）和紫藤紫藤凝集素（WFA）免疫染色。使用共聚焦显微镜对PV和WFA阳性细胞的数量进行计数，并使用Mann-Whitney U分析测试。与对照组相比，在8周DEP组中，小鼠的前额叶皮层，颞叶皮层，纹状体和小脑中HO-1的表达升高。与对照组相比，DEP组8周前额叶皮层和纹状体中SOD-2和XBP-1S的表达升高。与对照组相比，在4周和8周DEP组中，前额叶皮层，颞叶皮层，纹状体和小脑中的TNF-α表达升高。与对照组相比，DEP组8周嗅球和纹状体中Neurotrophin-3表达降低。与对照组相比，DEP组在8周内WFA密度增加。与对照组相比，DEP组4周的PV和PV + WFA密度降低。慢性DEP吸入可激活多个大脑区域的氧化应激和炎症。长期吸入DEP会增加PNN并减少中间神经元的数量，这可能与PM暴露相关的CNS功能障碍有关。