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Deciphering the spreading of neuropathologies in neuronal circuits using a high capacity microfluidics platform

Presented at: Neuroscience 2020
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Director of CNS research,Cellectricon AB
    Biography
      Sebastian joined Cellectricon in 2018 where he leads the company's CNS research. Together with his team, he works to devise novel concepts to generate human and rodent cell-based in vitro models that enable the discovery of new targets and compounds for neurodegenerative diseases. In addition, Sebastian holds a position at the University of Gothenburg where his research team aims to decipher the etiology of bipolar disorder, schizophrenia and Alzheimer's disease. Sebastian's research interests include neural development, neuroinflammation and neuronal circuit function and prior to joining Cellectricon, Sebastian did a Post-Doc at the Institute for Molecular Regenerative Medicine (PMU, Salzburg, Austria) and worked as guest researcher at the Natural and Medical Science Institute, Reutlingen, Germany. He did his PhD at the neurology department at the Heinrich-Heine University, Duesseldorf, Germany, where he, for the first time, combined pluripotent stem cell-derived neurons with microelectrode array technology in pre-clinical research.

    Abstract

    Misfolded and accumulated neurodegenerative disease associated proteins (NDAPs, such as tau and alpha-synuclein) represent the major pathological hallmark in Alzheimer’s and Parkinson’s disease patient brain cells. Compelling evidence indicate that spreading of NDAPs within the patient brain occurs via interconnected neurons. While progress in deciphering the mechanisms of neuronal uptake of NDAPs and NDAP-caused protein aggregation has been made, our knowledge about other cellular processes, such as axonal uptake and transport of NDAPs as well as neuron-to-neuron transfer of NDAPs, is still limited. In the presentation, I will present Cellectricon’s approach to decipher individual cellular processes that are occurring in progressive proteopathies in cortical neuronal circuits. We apply an experimental in vitro paradigm to generate compartmentalized neuronal cells by culturing primary mouse cortical neurons in high capacity microfluidic co-culture plates. By using fluorescently labelled, seed competent NDAPs and high-content imaging, we can assess NDAP axonal uptake, axonal transport and protein aggregation in cortical neurons. By combining our neuronal compartmentalisation approach with neuronal labelling techniques, we aim to decipher the spreading mechanisms of neuropathologies in neuronal circuits. We aim to provide insights into specific disease-relevant neuronal processes, which can pave the way for novel intervention approaches for modulation of progressive proteopathies.

    Learning Objectives:

    1. Introduce the audience the principles of progressive neurodegenerative diseases

    2. Present a concept that enables the assessment of specific cellular processes involved in progressive neurodegenerative diseases

    3. Present data obtained from Cellectricon´s high-capacity microfluidics platform showing alpha-synuclein axonal uptake, transport and caused protein aggregation in a sub-population of primary cortical neurons


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