Objective: To study the pathogenic potential of Gelsolin (GSN) and Secretogranin-3 (SCG3) in inducing Parkinsonian features.

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by progressive motor dysfunction. Our previous findings identified altered levels of fibrinogen, CFAH, gelsolin (GSN), SCG3, carnosine dipeptidase and Dkk3 proteins in the CSF of PD patients. In the brain, Gelsolin binds to the amyloid beta protein, inhibiting its fibrillization. SCG3 mends the early processing of the peptide hormones in the trans-Golgi network. PD being a multifactorial disorder, the present study aimed to investigate the role of gelsolin and SCG3 in PD pathogenesis by evaluating their effects on motor behavior in C57BL/6J mice.

Method: We used C57BL/6J mice (15-17 weeks; n = 8/experimental group; equal no. of males and females) for our study. They were divided into 5 groups: control, GSN 2.5µg, GSN 5µg, SCG3 2.5µg and SCG3 5µg. Following acclimatization and training, mice received a single injection of the proteins via i.p. Behavioural tests were performed 48 hours post-injection. Motor coordination and balance were assessed using pole test and rotarod test. The data was analysed using two-way ANOVA, followed by Tukey’s post hoc test using GraphPad Prism 10.1. *p<0.05 was considered significant.

Results: Mice treated with 2.5 µg gelsolin exhibited a significant increase in descend time in the pole test (Control vs Gelsolin 2.5µg; *p<0.05), indicative of motor impairment, whereas the GSN 5µg remained comparable with control. Rotarod performance parameters, including latency to fall, maximum rpm attained, and distance covered, were unaffected by both the doses of GSN. SCG3 2.5µg showed a significant decrease in all the rotarod performance parameters (Control vs SCG3 2.5µg; *p<0.05). A gender difference was noted in SCG3 5µg mice (male vs female; *p<0.05) on the rotarod, with males being more affected.

Conclusion: Administration of gelsolin produced partial alterations in motor behaviour while SCG3 caused significant alterations in motor coordination and endurance. The gender-specific changes in behaviour might explain the male-predominance of the disease. Thus, GSN and SCG3 administration might serve as models to induce motor deficits for studying PD pathogenesis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gelsolin-and-secretogranin-3-induce-parkinsonian-features-in-rodent-models/