SUN-040 A α-synuclein Mouse Model Of Parkinson Disease For Studying Fsh Effects

Abstract Disclosure: S.L. Sims: None. F. Tal: None. A. Gangadhar: None. A.A. Gumerova: None. Z.B. Tumoglu: None. J. Gimenez Roig: None. A.R. Pallapati: None. F. Sultana: None. S. Parte: None. V. Ryu: None. T. Yuen: None. M. Zaidi: None. R. Latif: None. Alpha-synuclein (α-syn) induced acute mouse models are an invaluable tool to study the pathogenesis, disease mechanisms and therapeutic strategies of Parkinson’s disease (PD). The aim of this study is to establish a working mouse model of PD using a mutant α-syn AAV overexpression system for probing the action of follicle-stimulating hormone (FSH) in PD. We used 12-week old male mice that were sterotactically injected into the right substantia nigra par compacta (SNC) AAV1/2 empty vector (EV) or AAV1/2 expressing a human mutated A53T - α-syn at concentration of 5 x 1012 gc /ml. To assess motor defects, the animals were subjected to behavioral studies at 5- and 11-week post injections using the classic Rotarod, and paw testing. We observed significant motor defect in A53T-injected mice comparing to their control littermates as evidenced by differences in times of first falls in variable and constant speed measurements at 11-week post injection suggesting that mutant A53T injected mice had impaired motor coordination. Immunofluorescent staining of brain SNC exhibited strong α-syn immunoreactivity in the ipsilateral SNC in contrast to no or minimal immunoreactivity in the contralateral SNC of A53T injected mice confirming overexpression of the mutant protein. The EV injected mice did not show any staining of the overexpressed α-syn. Furthermore, immunofluorescence for tyrosine hydroxylase (TH) - a marker of dopaminergic neurons - showed a significant decrease (>50%) in the number of TH positive neurons on the ipsilateral side of A53T injected animal versus no changes on the contralateral side or in the EV injected animals. These data suggest that overexpression of the mutant α-syn resulted in neuropathological damage of dopaminergic neurons in SNC. This mouse model of acute α-syn overexpression will allow us to examine the effects of gonadotropin hormones, especially of FSH, in the pathogenesis of PD. Presentation: Sunday, July 13, 2025