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α-Synuclein propagation leads to synaptic abnormalities in the cortex through microglial synapse phagocytosis

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Authors

Pérez-Acuña, Dayana; Shin, Soo Jean; Rhee, Ka Hyun; Kim, Sang Jeong; Lee, Seung-Jae

Issue Date
2023-10-17
Publisher
BMC
Citation
Molecular Brain, Vol.16(1):72
Keywords
Parkinson’s diseaseα-synucleinProtein aggregationMicrogliaSynapse degeneration
Abstract
The major neuropathologic feature of Parkinsons disease is the presence of widespread intracellular inclusions of α-synuclein known as Lewy bodies. Evidence suggests that these misfolded protein inclusions spread through the brain with disease progression. Changes in synaptic function precede neurodegeneration, and this extracellular α-synuclein can affect synaptic transmission. However, whether and how the spreading of α-synuclein aggregates modulates synaptic function before neuronal loss remains unknown. In the present study, we investigated the effect of intrastriatal injection of α-synuclein preformed fibrils (PFFs) on synaptic activity in the somatosensory cortex using a combination of whole-cell patch-clamp electrophysiology, histology, and Golgi-Cox staining. Intrastriatal PFF injection was followed by formation of phosphorylated α-synuclein inclusions in layer 5 of the somatosensory cortex, leading to a decrease in synapse density, dendritic spines, and spontaneous excitatory post-synaptic currents, without apparent neuronal loss. Additionally, three-dimensional reconstruction of microglia using confocal imaging showed an increase in the engulfment of synapses. Collectively, our data indicate that propagation of α-synuclein through neural networks causes abnormalities in synaptic structure and dynamics prior to neuronal loss.
ISSN
1756-6606
Language
English
URI
https://hdl.handle.net/10371/195795
DOI
https://doi.org/10.1186/s13041-023-01059-1
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College of Medicine/School of Medicine (의과대학/대학원)Neuroscience (뇌신경과학전공)Journal Papers (저널논문_뇌신경과학전공)
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