Researchers from the Paris Seine Neurosciences and Biological Adaptation and Ageing Unit have developed a simplified and robust neural network model based on human pluripotent stem cells grown in microfluidic chips.

Thanks to this human neuronal network model , they were able to observe that altered forms of alpha synuclein cause the appearance of pathological signs of Parkinson’s disease and multisystematic atrophy, another neurodegenerative disease. For each of these diseases, this protein aggregates differently and creates a characteristic “signature”.

They also showed that altered alpha-synuclein transfers from neuron to neuron and gradually affects the entire neural network and its function.

In the future, this model formed from stem cells may make it possible to study the effect of novel molecules capable of blocking altered forms of apha-synuclein in order to prevent their spread and neuronal degeneration.

The signature of these diseases may also be studied to facilitate their detection.

This study was published in Stem Cell Reports on January 10, 2019 and in a press release from CNRS and Inserm.

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Propagation of alpha-Synuclein strains within human reconstructed neuronal network. Simona Gribaudo, Philippe Tixador, Luc Bousset, Alexis Fenyi, Patricia Lino, Ronald Melki, Jean-Michel Peyrin, Anselme Louis Perrier. Stem Cell Reports, le 10 janvier 2019. Doi:10.1016/j.stemcr.2018.12.007

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Legend: Image of pathological alpha synuclein transfer from neurons to neurons. Cortical neurons derived human iPSC were differentiated in 2 compartmented microfluidic chambers allowing to recreate an oriented cortico-cortical human neuronal networks. Aggregates of recombinant alpha synuclein (red) introduced in the first neuronal compartment spreads to the MAP2 positive (blue) post synaptic neurons. Recombinant seeds triggers the aggregation of host encoded synuclein (green) in receiving neurons.