In a study titled ‘Neuroanatomical and cognitive biomarkers of alpha-synuclein propagation in a mouse model of synucleinopathy prior to onset of motor symptoms‘ Tullo et al. investigate the poorly understood neuroanatomical and behavioral consequences of alpha-synuclein (aSyn) propagation, which contributes to neurodegeneration in several disorders. The precise relationship between the progressive spreading of pathogenic aSyn and brain-region-specific atrophy, which underlies symptomatology, remains unknown.
Studying the Propagation of Toxic aSyn
Using a mouse model of synucleinopathy, the team obtained whole-brain atrophy patterns that are consistent with previous human clinical findings using small-animal magnetic resonance imaging (MRI). Additionally, early reversal learning deficits were revealed using automated touchscreen testing. To study the propagation of toxic aSyn, the team administered a single unilateral striatal PFF injection to M83 hemizygous mice. Some of the hemizygous M83 mice were also injected with phosphate-buffered saline (PBS). For immunohistochemistry, 14 mice were examined using IHC at 90 dpi as part of the team’s experimental design. The brains were extracted, fixed, sliced, and stained. Images were acquired and analyzed, and Visikol quantified the DAB-positive markers.
Discovery
In summary, Tullo et al. discovered that aSyn spreading from an injection site causes brain atrophy in connected regions, leading to cognitive deficits. The pattern of atrophy and cognitive deficits observed in mice mirror those seen in humans with Parkinson’s disease (PD). These findings suggest that MRI and touchscreen testing could be used to gauge disease progression and assess the efficacy of drug treatments for synucleinopathies, a group of neurodegenerative diseases characterized by the abnormal accumulation of aSyn in the brain.
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