Harnessing Neuroplasticity Genes to Combat Synucleinopathy Mediated Axonopathy
Abstract
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 (-syn)preformed fibril (PFF) synucleinopathy model exhibits a distinct stage of accumulation of -syninclusionsin tyrosine hydroxylase immunoreactive (THir) neurons in the substantia nigra pars compacta (SNpc) months prior to the ultimate degeneration of the nigrostriatal system.Inthe context of theearly phases of synucleinopathy in the-synPFF model, laser capture microdissection was used tocollectphosphorylated -syn(pSyn)immunoreactive SNpc neurons in PFF-injected rats and SNpc THir neurons in control-injectedrats.RNA was isolated and RNASeq used toidentify gene expression changesbetween SNpc neurons with and without pSyn inclusions. Results from male ratshave identified 102 candidate genes. Of these candidate genes, a subset associatedwith neuroplasticity or synaptic plasticity werevalidated in male and female rats with digital droplet PCR. Based on the validation results, we have selected SYN1 and CPLX2 as genes wewill designadeno-associated virusesto overexpressin the next phasewith the goal to mitigate neurodegeneration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2020
- Accession Number
- AD1111595
Entities
People
- Joseph P Patterson
Organizations
- Michigan State University