To investigate the role of ferroptosis in striatum damage induced by combined exposure of microplastics and manganese by establishing a mouse model following microplastics and manganese alone or combined exposure.
Forty SPF male C57 mice were randomly divided into control group, manganese exposure group, microplastics exposure group and combined exposure group. Neurobehavioral tests including rotarod test, open field test and sucrose preference test were performed. The contents of divalent iron, malondialdehyde and glutathione in striatum of mice were detected by using the kit. Western blotting was used to detect the protein expressions of SLC7A11, GPX4 and FPN1 in striatum of mice. Real-time PCR was performed to detect the expression of miR-124. Single factor analysis of variance was used for comparison of multiple groups of data, and LSD test was used for further pairwise comparison.
Behavioral tests showed that the residence time of the rotating rod (all P<0.001), the residence time in the central zone of open field test (all P<0.001), total distance of open field test (all P<0.001) and the sucrose preference rate (Pmanganese=0.010; Pmicroplastics<0.001) in manganese exposure group and microplastics exposure group decreased significantly compared with that of the control group. Compared with the manganese exposure group and microplastics exposure group, the residence time of the rotating rod, the residence time in the central zone of the open field test and the total distance of the open field test of combined exposure group decreased significantly (all P<0.001). In addition, the sucrose preference rate of the combined exposure group was lower than that of the manganese exposure group (P=0.001). At the same time, compared with the control group, the contents of Fe2+ in striatum of mice in manganese exposure group and microplastics exposure group increased (Pmanganese=0.002; Pmicroplastics=0.001), the contents of GSH decreased (Pmanganese=0.015; Pmicroplastics<0.001). The content of MDA in the striatum of mice in microplastics exposure group increased (P<0.001). Furthermore, the contents of Fe2+ and MDA in striatum of mice in combined exposure group were higher than those in manganese exposure group (PFe2+=0.004; PMDA<0.001) and microplastics exposure group (PFe2+=0.008; PMDA=0.007), while the content of GSH was lower than that in the manganese exposure group (P<0.001). The protein expressions of SLC7A11 in manganese exposure group (P=0.010) and microplastics exposure group (P=0.001) were lower than that in the control group. The protein expression of GPX4 in microplastics exposure group was lower than that in the control group (P=0.007), and the protein expression of GPX4 in the combined exposure group was lower than that in the manganese exposure group (P=0.006). The protein expressions of FPN1 in the manganese exposure group (P=0.005) and microplastics exposure group (P=0.002) were lower than that in the control group and the protein expression of FPN1 in the combined exposure group was significantly lower than those in the manganese exposure group (P=0.008) and microplastics exposure group (P=0.005). Compared with the control group, the expressions of miR-124 in striatum of mice in manganese exposure group (P=0.002) and microplastics exposure group (P<0.001) increased. At the same time, the expression of miR-124 in the striatum of mice in the combined exposure group was higher than those in the manganese exposure group and microplastics exposure group (all P<0.001).
Combined exposure of microplastics and manganese might lead to striatum damage in mice through the regulation of ferroptosis, and then cause motor dysfunction and anxiety-depression-like behavior.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |