Objective: This study further investigates the ameliorative effects of ECH on neurobehavioral abnormalities and nigrostriatal dopaminergic system impairment in α-synuclein preformed fibrils (α-Syn PFFs)-induced PD model, while also examining its therapeutic intervention on the core pathological lesion α-synuclein (α-Syn).

Background: Previous studies have demonstrated that echinacoside (ECH) exerts neuroprotective or restorative effects in the MPTP-induced Parkinson’s disease (PD) mouse model through anti-oxidative stress mechanisms and modulation of neurotrophic factor expressions.

Method: α-Syn PFFs were unilaterally injected into mouse striatum to induce PD. Groups: Sham control, PFFs model, ECH-L (10 mg/kg+PFFs), ECH-H (20 mg/kg+PFFs) (n=8). Motor function (pole tests) was assessed monthly. Terminal immunofluorescence evaluated nigrostriatal TH⁺ neurons and fibers, p-α-Syn aggregates.

Results: At 6 months, PFF mice showed prolonged pole descent time compared with baseline (26.94±16.87 vs 6.44±2.03 s, P=0.0035) and control (26.94±16.87 vs 12.25±4.57 s, P=0.046)..The survival rate (ipsilateral/contralateral) of SNpc TH⁺ neurons decreased 42.3% (P<0.0001), with striatal TH⁺ fibers reduced 56.6% (contralateral) and 62.7% (ipsilateral) (P<0.05) vs control. p-α-Syn fluorescence intensity in SNpc increased 5.4-fold(P = 0.017).Although the descent times of mice in ECH-H+PFFs group were longer than Sham group, those were markedly shorter than the model group (10.19 ± 4.77 s vs. 26.94 ± 16.87 s,P = 0.019).The survival rate of SNpc TH⁺ neurons in ECH-H group exhibited a 23.33% reduction compared to the Sham group but 75.67% higher significantly than the model group (P< 0.0001).Similarly the fluorescence of TH⁺ fiber instriatal of mice in ECH-H group exhibited 176% (contralateral; P = 0.0035) and 140% (ipsilateral; P = 0.046) higher than those in the model group, despite slight decreasel than the sham group (P > 0.05). Additionaly there was no significant change for the fluorescence of p-α-Syn in SNpc between ECH-H group with the sham group (P > 0.05) while 56.0% lower than the model group (P = 0.017).

Conclusion: High-dose ECH ameliorated behavioral deficits in α-Syn PFFs PD model mice and demonstrated partial neuroprotective efficacy against dopaminergic neurodegeneration induced by pathological α-synuclein aggregation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-neuroprotective-effects-of-echinacoside-on-%ce%b1-synuclein-fibril-induced-parkinsons-disease-mice-model/