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Harnessing Neuroplasticity Genes to Combat Synucleinopathy-Mediated Axonopathy

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[Technical Report, Annual Report]

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Michigan State University

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The earliest stages of synucleinopathy have been difficult to study due to the fact that most animal models of Parkinsons disease PD fail to recapitulate the progression of synucleinopathy to neurodegeneration. The alpha-synuclein alpha-syn preformed fibril PFF synucleinopathy model exhibits a distinct stage of accumulation of alpha-syn inclusions in tyrosine hydroxylase immunoreactive THirneurons in the substantia nigra pars compacta SNpc months prior to the ultimate degeneration of the nigrostriatal system. In the context of the early phases of synucleinopathy in the alpha-syn PFF model, laser capture microdissection was used to collect phosphorylated alpha-syn pSyn immunoreactive SNpc neurons in PFF-injected rats and SNpc THir neurons in control-injected rats. RNA was isolated and RNASeq used to identify gene expression changes between SNpc neurons with and without pSyn inclusions. Results from male rats have identified 102 candidate genes 24 expressed only with PFF treatment, and78 only in control animals. The known functions of these genes are being identified and those involved in neuroplasticity and confirmed with digital droplet PCR will be manipulated with designed adeno-associated viruses in the next phase with the goal to mitigate neurodegeneration.

Subject Categories:

  • Anatomy and Physiology

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[A, Approved For Public Release]