Abstract
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 25mg/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 25mg/kg PQ exposure, while that increased of acute 45mg/kg PQ exposure (P < 0.05). The number of endpoints decreased of acute 25mg/kg PQ exposure (P < 0.05). The process length became shorter both of acute 25mg/kg and 45mg/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 45mg/kg PQ exposure (P < 0.05). The number of endpoints increased and the process length became longer of acute 25mg/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 25mg/kg PQ exposure, whereas the number of the M2 phenotype of microglia increased during the early stage of acute 45mg/kg PQ exposure (P < 0.05). On day 39, compared with the control group, the expression of iNOS in the SN of acute 45mg/kg PQ exposure increased than of acute 25mg/kg exposure. The expression of Arg-1 of 25mg/kg PQ exposure was significantly increased (P < 0.05). On day 69, the expression of iNOS and ARG1 increased in the 25 and 45mg/kg PQ exposure groups. In summary, changes in microglia phenotypic differentiation were related to exposure dose and exposure time (P < 0.05).
Highlights
Paraquat (PQ) is a bipyridine cationic broad-spectrum herbicide that is a common cause of acute poisoning, with a mortality rate greater than 50% (Sun et al, 2018)
We demonstrated that acute exposure to PQ could affect the phenotypic differentiation of substantia nigra (SN) microglia in female rats
We observed the expression of ionized calcium-binding adaptor molecule 1 (Iba-1), Inducible nitric oxide synthase (iNOS) and Arginase enzyme 1 (ARG1) in the SN in female rats at different PQ doses and inferred the relationship between the change in the microglia polarization phenotype and the dose of acute PQ exposure at different times
Summary
Paraquat (PQ) is a bipyridine cationic broad-spectrum herbicide that is a common cause of acute poisoning, with a mortality rate greater than 50% (Sun et al, 2018). We observed the brain morphology and function of 26 patients with acute PQ poisoning and found that after 3–7 days of acute PQ poisoning, mild edema occurred in some brain regions, such as the frontal, parietal, basal ganglia and hippocampus. The myelin sheath in the substantia nigra pars reticularis, substantia nigra pars compacta, red nucleus and hippocampus showed certain structural abnormalities, the cerebral blood flow in the midbrain and frontal lobe decreased and the ratio of the brain metabolites inositol (MI), lipids (Lip) and phosphocreatine (Cr) in the basal ganglia increased (Wu et al 2012). Our previous studies have confirmed that acute PQ exposure leads to structural and functional abnormalities in the central nervous system
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