α-synuclein disrupts neuron network rhythmic activity when overexpressed in cultured neurons

by Kristian Leite
Doctoral thesis
Date of Examination:2021-02-09
Date of issue:2021-03-09
Advisor:Dr. Sebastian Kügler
Referee:Prof. Dr. Thomas Dresbach
Referee:Prof. Dr. Markus Zweckstetter
Persistent Address: http://dx.doi.org/10.53846/goediss-8468

 

 

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Abstract

English

Synucleinopathies are associated with a generalized slowing of the brain’s rhythmic activity, which co-occurs with dementia and has been connected with increased levels of α synuclein in both patients and test animals. In this study, the impact of increased levels of α synuclein on rhythmic activity was analyzed in vitro, with the intention of identifying the mechanisms behind the disruptive role of this protein. It was thus determined that increased levels of α-synuclein reduced the amount of structures involved in neuronal connectivity and reduced the levels of the signaling molecule cAMP. It was further determined that the reduction of burst frequency did not involve extracellular α-synuclein released by synuclein-overexpressing neurons, contradicting the results of previous studies. Finally, our study observed that in cases of tau protein or P123H β-synuclein mutant overexpression, the frequency of rhythmic activity was lowered alongside a simultaneous reduction of both structures involved in neuronal connectivity and levels of cAMP.
Keywords: Synuclein; Parkinson's disease; Tau protein; Network bursts; Network activity; Neurodegeneration; Connectivity; cAMP; P123H; Rhythmic activity; Automated analysis of neuronal activity; ImageJ analysis; AAV viruses; Calcium imaging; Fluorescence microscopy; Neuronal cell culture

Other Languages

Synuclein, Parkinson's disease, network activity, neuron, tau protein, neurodegeneration, connectivity, cAMP,
 
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