Exogenous α-synuclein hinders synaptic communication in cultured cortical primary rat neurons

G.C. Hassink, C.C. Raiss, I.M.J. Segers-Nolten, R.J.A. van Wezel, V. Subramaniam, J. le Feber (Corresponding Author), M.M.A.E. Claessens (Corresponding Author)

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Abstract

Amyloid aggregates of the protein α-synuclein (αS) called Lewy Bodies (LB) and Lewy Neurites (LN) are the pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. We have previously shown that high extracellular αS concentrations can be toxic to cells and that neurons take up αS. Here we aimed to get more insight into the toxicity mechanism associated with high extracellular αS concentrations (50-100 μM). High extracellular αS concentrations resulted in a reduction of the firing rate of the neuronal network by disrupting synaptic transmission, while the neuronal ability to fire action potentials was still intact. Furthermore, many cells developed αS deposits larger than 500 nm within five days, but otherwise appeared healthy. Synaptic dysfunction clearly occurred before the establishment of large intracellular deposits and neuronal death, suggesting that an excessive extracellular αS concentration caused synaptic failure and which later possibly contributed to neuronal death.
Original languageEnglish
Article numbere0193763
Number of pages21
JournalPLoS ONE
Volume13
Issue number3
DOIs
Publication statusPublished - 22 Mar 2018

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Synucleins
animal communication
Neurons
Rats
Deposits
neurons
Communication
death
Amyloidogenic Proteins
Lewy Bodies
synaptic transmission
Aptitude
neurites
Parkinson disease
Poisons
Protein S
rats
protein aggregates
Neurites
amyloid

Cite this

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abstract = "Amyloid aggregates of the protein α-synuclein (αS) called Lewy Bodies (LB) and Lewy Neurites (LN) are the pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. We have previously shown that high extracellular αS concentrations can be toxic to cells and that neurons take up αS. Here we aimed to get more insight into the toxicity mechanism associated with high extracellular αS concentrations (50-100 μM). High extracellular αS concentrations resulted in a reduction of the firing rate of the neuronal network by disrupting synaptic transmission, while the neuronal ability to fire action potentials was still intact. Furthermore, many cells developed αS deposits larger than 500 nm within five days, but otherwise appeared healthy. Synaptic dysfunction clearly occurred before the establishment of large intracellular deposits and neuronal death, suggesting that an excessive extracellular αS concentration caused synaptic failure and which later possibly contributed to neuronal death.",
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AU - Raiss, C.C.

AU - Segers-Nolten, I.M.J.

AU - van Wezel, R.J.A.

AU - Subramaniam, V.

AU - le Feber, J.

AU - Claessens, M.M.A.E.

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