Acute exposure to paraquat affects the phenotypic differentiation of substantia nigra microglia in rats

The toxicity of the bipyridine cationic herbicide paraquat (PQ) to the lung and kidneys has been widely documented, but the acute toxic effects of PQ on the nervous system have received little attention. This study aimed to explore the changes in the phenotypic differentiation of microglia in rats caused by acute PQ exposure. As results, acute PQ exposure induced pyknosis, edema, and apoptosis in substantia nigra neurons. Immunohistochemistry and western blotting showed that, on day 18, with the increase of exposure dose, the number of Iba-1-positive cells presented an increasing trend with no statistically significant difference among the groups (P > 0.05). Compared with the control group, the process length of Iba-1-positive cells decreased of acute 25 mg/kg PQ exposure on day 18 (P < 0.05). Compared with the control group, on day 39, the number of Iba-1-positive cells in the SN decreased of acute 25 mg/kg PQ exposure, while that increased of acute 45 mg/kg PQ exposure (P < 0.05). The number of endpoints decreased of acute 25 mg/kg PQ exposure (P < 0.05). The process length became shorter both of acute 25 mg/kg and 45 mg/kg PQ exposure (P < 0.05). On day 69, compared with the control group, the number of Iba-1-positive cells in the SN significantly increased of acute 45 mg/kg PQ exposure (P < 0.05). The number of endpoints increased and the process length became longer of acute 25 mg/kg PQ exposure (P < 0.05). Then, the mean fluorescence intensity of inducible nitric oxide synthase (iNOS) and arginine 1 (ARG1) was compared. The number of the M1 phenotype of microglia increased during the early stage of acute 25 mg/kg PQ exposure, whereas the number of the M2 phenotype of microglia increased during the early stage of acute 45 mg/kg PQ exposure (P < 0.05). On day 39, compared with the control group, the expression of iNOS in the SN of acute 45 mg/kg PQ exposure increased than of acute 25 mg/kg exposure. The expression of Arg-1 of 25 mg/kg PQ exposure was significantly increased (P < 0.05). On day 69, the expression of iNOS and ARG1 increased in the 25 and 45 mg/kg PQ exposure groups. In summary, changes in microglia phenotypic differentiation were related to exposure dose and exposure time (P < 0.05).