Background
α-Synuclein is a protein that is abundantly expressed in the presynaptic terminals of neurons. In Parkinson's disease, α-synuclein misfolds and aggregates, forming insoluble fibrillar structures called Lewy bodies– a hallmark pathological feature of Parkinson's disease, contributing to dopaminergic neuron degeneration.
By examining the distribution and aggregation patterns of α-synuclein, researchers can gain insights into the mechanisms underlying the formation of Lewy bodies and their role in neuronal degeneration.
Tyrosine Hydroxylase (TH) is an enzyme responsible for catalyzing the rate-limiting step in the biosynthesis of dopamine. Dopaminergic (TH-positive) neurons are vulnerable to degeneration in Parkinson's disease. Therefore, monitoring TH-positive (dopaminergic) neurons can provide insights into the extent of neuronal loss and dysfunction in different brain regions affected by Parkinson's disease. Given their interconnected nature, we measure both α-Synuclein and TH when investigating Parkinson’s disease pathology.
How We Study α-synuclein & Tyrosine Hydroxylase
α-Synuclein and TH Imaging and Identification
Leveraging tissue clearing, light sheet imaging, and AI-powered quantification, Translucence Biosystems provides comprehensive data into α-synuclein & Tyrosine Hydroxylase distribution involved in Parkinson's disease and related neurodegenerative disorders.
Translucence Biosystems employs our modified iDISCO+ tissue clearing protocol to render intact samples optically transparent, labeling α-synuclein and Tyrosine Hydroxylase immunoreactivity across the whole brain.
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Translucence then employs our AI-powered Translucence Teravoxel ToolKit (3TK) software to segment α-synuclein & Tyrosine Hydroxylase across whole mouse brains. Segmenting of α-synuclein & Tyrosine Hydroxylase using AI-powered workflows allows us to pull out metrics of intensity, shape, density, and size.
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Brain-Wide Quantification of α-Synuclein and Tyrosine Hydroxylase
Then, using our VoxelsTM software, we computationally warp each brain and its segmented objects to the Allen Reference Brain, allowing for detailed examination of object-level metrics across hundreds of brain regions. For α-synuclein, we segment and warp data to analyze the spatial distribution and density across the brain while for Tyrosine Hydroxylase (TH), we employ integrated intensity volume quantification, which generates regional integrated intensity data. Measuring both of these targets offers comprehensive insights into their regional expression patterns, facilitating comparisons across different experimental conditions or disease models.
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Summary
By leveraging tissue clearing, light sheet imaging, and AI-powered 3D quantification, Translucence Biosystems is able to generate whole-brain measurements of ɑ-synuclein & Tyrosine Hydroxylase for robust insights into Parkinson’s Disease pathology in response to various experimental manipulations.
