Activation and mechanism of microglia in Tourette syndrome
Objective To investigate the activation and mechanism of microglia(MG)in Tourette syndrome(TS)rats induced by 3,3'-aminodipropionitrile(IDPN).Methods Thirty six male Sprague Dawley rats were randomly divided into a TS group and a Sham group(Sham group),with 18 rats in each group.The TS group received intraperitoneal injection of IDPN for 7 days,with the dose of 300mg/(kg·d),while the Sham group received intraperitoneal injection of physiological saline for 7 days,with the dose of 5mL/(kg·d).Double immunofluorescence staining was used to detected the expression of inducible nitric oxide synthase(iNOS),a marker protein of M1 type microglia,and its co-localization with Iba-1(a specific marker for microglial activation)in rat striatum,as well as the expression of arginase 1(Arg-1)and its co-location with Iba-1 in M2 microglia.The expression levels of iNOS,Arg-1 in rat striatal tissues were quantified by enzyme-linked immunosorbent measurement(ELISA),real-time PCR(qRT-PCR),meanwhile the expression levels of inflammatory cytokines tumor necrosis factor α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)were detected.Results Immunofluorescence double staining showed that the positive expressions of Iba-1 and iNOS in striatum of TS group were enhanced and co-located compared with Sham group,while the positive expression of Iba-1 and Arg-1 in striatum of TS group decreased and showed co-localization.The ELISA results showed that compared with the Sham group,the TS group had a significant increase in the content of M1 type MG marker protein iNOS(t=5.796,P＜0.001),a significant decrease in the content of M2 type MG marker protein Arg-1(t=4.348,P＜0.01),and a significant increase in inflammatory factors,including TNF-α,IL-6 and IL-10(t=5.654,5.748,8.231,P＜0.001).The qRT-PCR results showed that compared with the Sham group,the mRNA expression level of iNOS,a M1 type MG marker protein,was significantly increased in the TS group(t=9.914,P＜0.001),while the mRNA expression level of Arg-1,a M2 type MG marker protein,was significantly reduced(t=4.390,P＜0.01),and the mRNA expression levels of inflammatory factors in the TS group,including TNF-α,IL-6 and IL-10 were significantly increased(t=12.056,14.147,13.350,P＜0.001).Conclusion TS rats induced by IDPN exhibit MG activation,with M1 type MG upregulated and M2 type MG downregulated,thereby mediating neuroinflammation.
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