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OBJECTIVE: To explore the effects of acute paraquat (PQ) exposure on the phenotypic polarization of hippocampal microglia and its mechanism. METHODS: An acute PQ exposure rat model was established. Male SD rats were exposed to 0, 5, 25, and 50 mg/kg PQ, and brain hippocampal tissue was collected after 1, 3, and 7 days of exposure, respectively. Hippocampal pathological changes were examined by H&E staining, and immunohistochemistry (IHC) was used to detect changes in the number of Iba-1-positive cells, the average number of endpoints, and the average process length. The protein expression of Iba-1 was detected by western blotting. BV-2 microglia were treated with 0, 0.01, 0.025, 0.05, or 0.1 µmol/L PQ for 24 h. ELISA and western blotting assays were performed to detect the expression of TNF-α and IL-1ß in vivo and in vitro. The M1 microglia marker iNOS, the M2 microglia marker Arg-1, and the p-JAK2 and p-STAT3 protein were detected by western blotting. JAK2/STAT3 pathway activation role in regulating microglia phenotypic polarization was further validated in vivo and in vitro by JAK2-specific inhibitor AG490 administration. RESULTS: After acute PQ exposure, hippocampal neurons showed pathological changes such as loose arrangement and nuclear pyknosis, the number of Iba-1 positive cells and the expression of Iba-1 protein increased, and the average number of endpoints and average process length of microglia decreased. Histological examination revealed that compared with the control group, in the 50 mg/kg PQ group on the 3rd and 7th day, the expression of TNF-α, IL-1ß, and iNOS significantly increased, while that of Arg-1 significantly decreased. p-JAK2 and p-STAT3 expression significantly increased in the 50 mg/kg PQ group on the 1st, 3rd, and 7th day. In vitro, compared with the control group, the expression of TNF-α, IL-1ß, iNOS, p-JAK2, and p-STAT3 significantly increased, while Arg-1 expression was significantly reduced in the 0.025, 0.05, and 0.1 µmol/L PQ groups. After AG490 administration, the expression levels of p-JAK2, p-STAT3, iNOS, TNF-α, and IL-1ß in the AG490 +PQ group were significantly inhibited in vivo and in vitro compared with the PQ-only group. On the contrary, Arg-1 expression was significantly increased. CONCLUSION: Our results suggest that acute PQ exposure may induce M1-type polarization of hippocampal microglia by activating the JAK2/STAT3 pathway, which in turn releases pro-inflammatory factors such as TNF-α and IL-1ß, leading to hippocampal inflammatory damage.
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The combination of the two hot topics of spin-orbit coupling and honeycomb lattices leads to the appearance of fascinating issues. In this paper, we investigate the existence and stability of vector gap solitons of spin-orbit-coupled Bose-Einstein condensates loaded in honeycomb optical lattices. The existence and stability of vector gap solitons are highly sensitive to the properties of interspin and intraspin atomic interaction. We numerically obtain the parametric dependence of the existence of vector gap solitons both in the semi-infinite gap and in the first gap. Since only dynamically stable localized modes in nonlinear systems are likely to be generated and observed in experiments, we examine the stability of the vector gap solitons by using the direct evolution dynamics, and obtain the phase diagram of stable and unstable vector gap solitons on the parameter plane of interspin and intraspin atomic interactions.
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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).
Assuntos
Herbicidas , Paraquat , Animais , Herbicidas/metabolismo , Microglia , Paraquat/toxicidade , Fenótipo , Ratos , Substância NegraRESUMO
The stability properties of dark solitons in quasi-one-dimensional Bose-Einstein condensate (BEC) loaded in a Jacobian elliptic sine potential with three-body interactions are investigated theoretically. The solitons are obtained by the Newton-Conjugate Gradient method. A stationary cubic-quintic nonlinear Schrödinger equation is derived to describe the profiles of solitons via the multi-scale technique. It is found that the three-body interaction has distinct effect on the stability properties of solitons. Especially, such a nonlinear system supports the so-called dark solitons (kink or bubble), which can be excited not only in the gap, but also in the band. The bubbles are always linearly and dynamically unstable, and they cannot be excited if the three-body interaction is absent. Both stable and unstable kinks, depending on the physical parameters, can be excited in the BEC system.