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AimsThe accumulation of α-synuclein in astrocytes in Parkinson's disease is considered to be secondary to neuronal accumulation. The aim of this study to identify whether astrocytes accumulate small α-synuclein aggregates before or after neurons in the nigrostriatal pathway.MethodsFixed serial midbrain and striatal sections from M83 A53T transgenic mouse model of Parkinson's disease and wild-type controls were histologically processed for multiplex labelling of α-synuclein and astrocytic markers and astrocyte quantitation performed on digital images using QuPath software.ResultsThe density of astrocytes within the substantia nigra pars compacta was approximately 30% greater compared with other sampled regions (p ConclusionsThese data suggest that small α-synuclein aggregates are normally cleared by astrocytes and that the substantia nigra pars compacta requires more astrocytic support for this function than other midbrain dopaminergic regions or the striatum. This adds another vulnerability factor to those already known for the substantia nigra with early deficits in clearance of small α-synuclein aggregates by astrocytes associated with increased astrocytic reactivity in the A53T transgenic mouse model.
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