Event Abstract

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

  • 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


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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

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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