Preclinical WebsiteClinical Website

Synuclein Model Overview

For this Parkinson's disease model, we perform stereotaxic inoculation of recombinant preformed fibrils (PFFs) into the Anterior Olfactory Nucleus (AON) of M83 mice [B6;C3-Tg( Prnp SNCA A53T )83Vle/J]. The rationale for targeting the AON includes:

  • It is one of the earliest sites to demonstrate alpha-synuclein (α-synuclein; α-syn) pathology (Lewy bodies) in human Parkinson's disease (Braak Stage 1)
  • Non-motor symptoms associated with the limbic system (e.g. hyposmia/anosmia, sleep alterations) are prevalent, early symptoms of Parkinson's disease (PD)
  • The AON is connected to several ipsilateral & contralateral brain regions, including direct (1st order) connections to olfactory bulb, amygdala, piriform cortex, and higher order connections, such as the entorhinal cortex and hippocampus; many of these regions are highly vulnerable to neurodegeneration

Spatial pattern of spread of α-synuclein pathology in this animal model of Parkinson's disease following stereotaxic injection of recombinant preformed fibrils into the anterior olfactory nucleus (AON) of M83 transgenic mice.

A significant advantage of this rodent model is that it reproduces many aspects of human Parkinson's disease, including: 

  • Highly reproducible spreading of α-synuclein in a well-defined spatiotemporal pattern, resulting in extensive α-synuclein pathology in neuronal cell bodies and neurites 
  • Strong neuroinflammation (microgliosis and astrogliosis)
  • Neurodegeneration & regional brain atrophy
  • Measurable behavioral changes, such as alterations of sleep/wake cycles
  • Amenable to disease modification via therapeutic intervention

Synuclein Model Generation

A general schema for synuclein PFF animal model generation is:

Parkinson's Disease - Synuclein PFF injection AON process
 A stereotaxic surgery setup with a rodent, commonly used in neurological research to administer treatments with precision to specific brain regions, particularly for Parkinson's Disease (PD) studies.

We have in-licensed the M83 transgenic (tg) mice which show α-syn overexpression. As a Preclinical Neuroscience CRO, we maintain a well-established breeding colony of these transgenic alpha-synuclein mice in-house at Biospective, allowing us to conduct large-scale (>100 mice) studies.

For this specific rodent model, we breed and age M83+/- male mice to 8-12 weeks-of-age. We then perform stereotaxic injection of sonicated, recombinant human alpha-syn PFFs into the AON. We use digital stereotaxic devices with automated microinjectors for high accuracy & precision.

This animal model is highly reproducible with a nearly 100% success rate of synuclein PFF seeding.

Our Synuclein Mouse Model Validated Measures

A pair of brain tissue sections processed with immunohistochemistry (IHC) to highlight phosphorylated alpha-synuclein, which is relevant in the context of Parkinson's Disease research

Phosphorylated alpha-synuclein immunohistochemistry staining of the ipsilateral (left) and contralateral (right) piriform cortex at 12 weeks post-injection following unilateral stereotaxic inoculation of alpha-synuclein preformed fibrils (PFFs) into the anterior olfactory nucleus of an M83+/- transgenic mouse.

Learn more about our characterization of this model, our validated measures, and our Preclinical Neuroscience CRO services.

Discover more of our Parkinson's Disease Models


Has a therapeutic effect been shown in the α-Synuclein Fibril Seeding (Limbic System) model?

Yes. That is a key advantage of this rodent model. We have a high level of alpha-synuclein pathology, microgliosis, astrogliosis, and neurodegeneration, so we can demonstrate a drug effect.

A good example can be found in the paper: Nordstrõm et al., ABBV-0805, an novel antibody selective for soluble aggregated α-synuclein, prolongs lifespan and prevents buildup of α-synuclein pathology in mouse models of Parkinson's disease. Neurobiol. Dis., 161: 105543, 2021; doi:10.1016/j.nbd.2021.105543.

Does Biospective observe neurodegeneration in the α-Synuclein Fibril Seeding (Limbic System) model?

Yes. We see highly elevated levels of neurofilament light in the plasma and CSF of the alpha-synuclein fibril seeding mice.

AON Plasma NfL Graph

We also observe highly significant brain atrophy of multiple regions, such as the piriform cortex and entorhinal cortex, via in vivo MRI (see Brain atrophy analysis in rodent models of neurodegenerative diseases). 

Are "activated" microglia present in the α-Synuclein Fibril Seeding (Limbic System) model?

Yes. In fact, we have specifically characterized activated microglia in these Parkinson's disease mice in our Presentation - Microglial activation in an α-synuclein mouse model of Parkinson's disease.

What is a "preformed fibril" (PFF)?

Preformed fibrils (PFFs) are recombinant, monomeric proteins (e.g. alpha-synuclein or tau) are incubated under specific conditions to generate aggregated, misfolded fibrils. These fibrils are then sonicated to generate short fibrils that can be used for in vitro or in vivo studies.

Is the α-Synuclein Fibril Seeding (Limbic System) model readily available for studies?

Yes. We maintain a well-established breeding colony of M83 transgenic synuclein mice so that mice are readily available for studies. Mice are typically aged to 8-12 weeks prior to inoculation with α-synuclein PFFs.

How do you measure sleep in the α-Synuclein Fibril Seeding (Limbic System) model?

We use a non-invasive, high-throughput system called PiezoSleep to measure sleep in these Parkinson disease mice (learn more about how we non-invasively measure sleep in mouse models). We find highly reproducible, progressive alterations of the sleep/wake cycles in this model. We commonly use this test to evaluate putative disease-modifying therapeutic agents in this mouse model.

More Information

Let us know what you’re interested in. Our team will be happy to discuss with you!

Email us at i[email protected] or simply complete & submit the form below. 

Phone Number*
Affiliation (Company/University)*

Your privacy is important to us. We will protect your data as outlined in our Privacy Notice.

I agree to the terms in the Privacy Notice*

We use necessary cookies to make our site work. We also use other cookies to help us make improvements by measuring how you use the site or for marketing purposes. You have the choice to accept or reject them all. For more detailed information about the cookies we use, see our Privacy Notice.