Effects of inhaled particulate matter on the central nervous system in mice

Abstract

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.