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 (a-syn) preformed fibril (PFF) synucleinopathy model exhibits a distinct stage of accumulation of a-syn inclusions in tyrosine hydroxylase immunoreactive (THir) neurons 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 a-syn PFF model, laser capture microdissection was used to collect phosphorylated a-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 and female rats have identified 326 candidate transcripts. Of these candidates, Gap43, a gene related to neuroplasticity/synaptic plasticity, was selected to be overexpressed via adeno-associated viral vector. The overall goal is to determine if Gap43 expression is sufficient to mitigate neurodegeneration in a model of synucleinopathy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2024
- Accession Number
- AD1229000
Entities
People
- Caryl Sortwell
- Joseph P Patterson
Organizations
- Michigan State University