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Rose B. Creed, Adeel A. Memon, Matthew S. Goldberg, Matthew S. Goldberg, Department of Neurology, University of Alabama at Birmingham, 1720 University Blvd, Birmingham, AL 35294
Alpha-synuclein pathology is one of the main pathological hallmarks of Parkinson’s disease (PD). Mutations in the alpha-synuclein gene are causally linked to dominantly inherited forms of PD. Although the cause of PD remains uncertain, mitochondrial dysfunction is implicated in both familial and idiopathic PD. Some of the most widely used animal models of PD are based on toxins that inhibit mitochondrial complex I, such as MPTP and rotenone. There is substantial evidence that abnormal forms of alpha-synuclein cause mitochondrial dysfunction and this could be a common pathogenic mechanism for idiopathic and familial forms of PD. Recently, promising PD animal models have been generated by injection of pre-formed fibrils (PFF) of purified recombinant alpha-synuclein into the striatum or the substantia nigra of rats or mice. The effects of intracranial injection of alpha-synuclein PFFs on mouse brain mitochondria remains to be determined. To help fill this knowledge gap, we performed unilaterial striatal injections of C57/BL6 mice with alpha-synuclein monomer or PFFs and euthanized the mice at 3 months and 6 months post injection to harvest brain tissue for analysis of mitochondrial function and abundance. In PFF but not monomer-injected mice, we observed prominent immunoreactivity using antibodies specific for alpha-synuclein phosphorylated at serine 129, which is a relatively selective marker of synuclein pathology in human postmortem brains and animal models. Functional analysis of striatal mitochondria revealed significantly altered complex I activity in the PFF-injected mice at 6 months post-injection, but not at 3 months post-injection. These results indicate that the alpha-synuclein preformed fibril intracranial injection animal model of PD may be useful for mechanistic and therapeutic studies involving mitochondrial dysfunction caused by aggregated forms of alpha-synuclein.
Presenter: Sindhu Komaragiri
Institution: University of Alabama at Birmingham
Type: Poster
Subject: Animal Sciences
Status: Approved
