Study on Parkinson's disease-like pathology induced by Lrrk2 R1628P transgenic mouse's urine exosomes
Aim:To observe the Parkinson's disease(PD)-like pathology induced by injection of Lrrk2 R1628P trans-genic mouse urine exosomes into the striatum.Methods:Urine exosomes were extracted from wild type(WT)and Lrrk2 R1628P mice,and the expressions of urine exosome markers TSG101 and CD81,and phosphorylated glycogen synthetase ki-nase-3β at site Y216(pGSK-3β-216)were detected by Western blot.The urine exosomes of WT mice(C57-WT group)and Lrrk2 R1628P mice(C57-Lrrk2 group)were injected into the striatum of C57 mice(8 in each group),and the behavioral function was analyzed by beam working test,hanging-wire grip test,rotarod test and open field test before injection,and 1 month,3 months,6 months after injection.The deposition of phosphorylated α-syn(pα-syn)in the brain was analyzed by immunohistochemical staining,and the expression level of pα-syn in the brain was evaluated by Western blot.Results:Compared with WT mice,the expressions of TSG101 and CD81 in urine exosomes of Lrrk2 R1628P mice were not signifi-cantly different(P>0.05),but the expression of pGSK-3β-216 was higher(P<0.001).In C57-Lrrk2 group,PD-like be-havioral phenotype was observed(P<0.001),pα-syn was deposited in the cortex,striatum and substantia nigra,and the ex-pression of pα-syn in the brain was(0.44±0.06),while none in C57-WT group(P<0.001).Conclusion:PD-like pa-thology can be induced by injecting urinary exosomes of Lrrk2 R1628P transgenic mice into the striatum.
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