Event Abstract

Back to Event

The effect of ɑ-synuclein preformed fibrils on network activity development in cultured cortical neurons

Fikret Emre Kapucu1, 2* and Poul H. Jensen1, 2
  • 1 Danish Research Institute of Translational Neuroscience (DANDRITE), Denmark
  • 2 Aarhus University, Department of Biomedicine, Denmark

Misfolded protein aggregates have been linked with several neurodegenerative diseases. Parkinson disease (PD) is highly associated with the aggregation of α-synuclein and the related factors disturbing the homeostatic mechanisms[1]. Aggregated amyloid-type fibrillar forms of α-synuclein accumulate in intra-neuronal Lewy body inclusions and are the pathological hallmark of PD as well as other type of α-synucleinopathies, i.e., dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) [2]. Accumulation of pathologic α-synuclein leads reduction in synaptic proteins, progressive impairments in neuronal excitability and connectivity, and eventually, neuron death [3]. The effect of α-synucleinopathies on cellular electrophysiology has been shown in several studies. Some of them assessed cellular level responses, thus, focused on single cells [4, 5]. For example, Betzer et al. [ 4] showed the importance of investigating cytosolic calcium concentrations as an early indicator for PD. On the other hand, the effects of aggregated insoluble α-synuclein also shown at network level [3, 6]. Synaptic impairment can be observed in mature primary rat cortical neurons with the inclusion of fibrils [6] ; consequently, network level activity diminishes. To our knowledge, functional network development of primary cultures with the inclusion of insoluble α-synuclein aggregates have not been studied by using microelectrode arrays before. In this work, functional development of primary mouse cortical cultures is tracked with correlated spectral entropy (CorSE) method as in Kapucu et al. [7, 8]. Then, we evaluate the results together with the parallel cytosolic calcium measurements collected at the same measurement day (Figure 1). This study would provide an important preliminary insight on the effect of α-synuclein assemblies on cellular mechanisms and concurrent effects on network development.

Figure 1
Image

References

[1] Nussbaum RL, Genetics of Synucleinopathies. Cold Spring Harb Perspect Med, 2017.
[2] Leonid B, Jessica WW, Vladimir N. et al. (2012) α-Synuclein misfolding and Parkinson's disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. https://doi.org/10.1016/j.bbadis.2011.10.002.
[3] Volpicelli-Daley LA, Luk KC, Patel TP, et al. (2011) Exogenous α-synuclein fibrils induce Lewy Body pathology leading to synaptic dysfunction and neuron death. Neuron. 72(1):57-71. https://doi:10.1016/j.neuron.2011.08.033.
[4] Betzer C, Lassen LB, Olsen A. et al. (2018) Alpha-synuclein aggregates activate endoplasmic reticulum calcium ATPase leading to calcium dysregulation. EMBO Reports (In press)
[5] Schmidt F, Levin J, Kamp F, Kretzschmar H, Giese A, et al. (2012) Single-channel electrophysiology reveals a distinct and uniform pore complex formed by α-synuclein oligomers in lipid membranes. PLOS ONE 7(8): e42545. https://doi.org/10.1371/journal.pone.0042545
[6] Peelaerts W, Bousset L, Van der Perren A, et al. (2015) α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature 522:340-344. http://dx.doi.org/10.1038/nature14547
[7] Kapucu FE, Välkki I, Mikkonen JE et al (2016) Spectral entropy based neuronal network synchronization analysis based on microelectrode array measurements. Front Comput Neurosci 10:112. https://doi.org/10.3389/fncom.2016.00112
[8] Kapucu FE, Tanskanen JMA, Christophe F et al (2017) Evaluation of the effective and functional connectivity estimators for microelectrode array recordings during in vitro neuronal network maturation. In: Eskola H, Väisänen O, Viik J et al (eds) European Medical and Biological Engineering Conference, Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (EMBEC & NBC 2017), Tampere, Finland, June 2017. IFMBE Proceedings, vol. 65, Springer, Singapore, pp. 1105-1108. https://doi.org/10.1007/978-981-10-5122-7_276

Keywords: alpha-Synuclein, preformed fibrils, cortical culture, Micro electrode arrays (MEAs), Network analysis

Conference: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.

Presentation Type: Poster Presentation

Topic: Neural Networks

Citation: Kapucu F and Jensen PH (2019). The effect of ɑ-synuclein preformed fibrils on network activity development in cultured cortical neurons. Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays. doi: 10.3389/conf.fncel.2018.38.00023

Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.

The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.

Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.

For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.

Received: 22 May 2018; Published Online: 17 Jan 2019.

* Correspondence: Dr. Fikret Emre Kapucu, Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus, Denmark, emre.kapucu@tuni.fi