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Table of Contents

Table of Contents

Abstract
01. Presentation Overview
Presentation
01. Introduction02. Microglial Classification03. Machine Learning Model04. Activation Score05. Alpha-Synuclein Mouse Model06. Microglia Density07. Microglia Activation08. Activation vs. Density09. Mouse Model Activation Score10. Clustering11. Summary

α-Synuclein preformed fibril (PFF) inoculation into a M83+/- transgenic mouse model of Parkinson's disease:

  • Transgenic mice overexpressing α-synuclein with an A53T mutation
  • Injection of recombinant, human PFFs into the Anterior Olfactory Nucleus (AON)
  • Seeding and spreading of pathology to connected brain regions
  • Progressive neurodegeneration (including MRI brain atrophy and elevated NfL in plasma & CSF)
  • Strong microgliosis and astrogliosis in regions of ∝-synuclein pathology
α-Synuclein (p-Syn) pathology seen in the piriform cortex of M83+/- PFF mice after unilateral stereotaxic injection of α-synuclein PFFs into the AON.
Microgliosis (Iba-1) seen in the piriform cortex of M83+/- PFF mice after unilateral stereotaxic injection of α-synuclein PFFs into the AON.
Neurodegeneration (NeuN) seen in the piriform cortex of M83+/- PFF mice after unilateral stereotaxic injection of α-synuclein PFFs into the AON.
Astrogliosis (GFAP) seen in the piriform cortex of M83+/- PFF mice after unilateral stereotaxic injection of α-synuclein PFFs into the AON.

α-Synuclein (p-Syn) pathology [top left], microgliosis (Iba-1) [top right], neurodegeneration (NeuN) [bottom left], and astrogliosis (GFAP) [bottom right] seen in the piriform cortex of M83+/- PFF mice after unilateral stereotaxic injection of α-synuclein PFFs into the AON.

Please note that we provide a link to all of our Parkinson's disease and other CNS disease models on the last page of this presentation.

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We have applied this microglial morphology analysis  to our alpha-synuclein preformed fibril seeding and spreading model of Parkinson's disease that we routinely use for therapeutic efficacy studies. 

For model generation, we breed and age hemizygous M83 mice to 8 to 12 weeks-of-age. We then perform stereotaxic inoculation of sonicated preformed fibrils into the anterior olfactory nucleus (AON). This model shows microglial activation in a spatiotemporal pattern that follows the synuclein pathology.

For this study, we used Iba-1 IHC stained tissue sections from PBS control and PFF injected mice at different time points post-inoculation.

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