Biology subjects

König, A.

Publications and source records attributed to König, A..

3 recordsLinked to original sources

bioRxiv2022

High-and Low-Frequency Deep Brain Stimulation in the Subthalamic Nucleus differentially modulate Response Inhibition and Action Selection in Parkinson's Disease

BackgroundWhile deep brain stimulation (DBS) in the subthalamic nucleus (STN) improves motor functions in Parkinsons disease (PD), it has also been associated with increased impulsivity. MethodsA combined approach of eye-tracking and high-density EEG was used to investigate how high- and low-frequency DBS impact impulsive actions in the antisaccade task in a cohort of ten persons with PD. Computational modelling of the behavioral outcomes allowed a nuanced insight into the effect of DBS on response inhibition and action selection processes. Results: Against our expectations, both 130 Hz- and 60 Hz-DBS improved response inhibition as both resulted in a reduced rate of early reflexive errors. Correspondingly, DBS with both frequencies led to increased desynchronization of beta power during the preparatory period which may be a correlate of anticipatory activation in the oculomotor network. Low-frequency DBS additionally was associated with increased midfrontal theta power, an established marker of cognitive control. While higher midfrontal theta power predicted longer antisaccade latencies in off-DBS state on a trial-by-trial basis, 130 Hz-DBS reversed this relationship. As informed by the computational model, 130 Hz-DBS further led to a shift in the speed-accuracy trade-off causing an acceleration and error-proneness of actions later in the trial. ConclusionsOur results disentangle the impact of DBS on early and late impulsive actions. Only 130 Hz-DBS may disrupt theta-mediated cognitive control mechanisms via medial frontal - STN pathways that are involved in delaying action selection. 60 Hz-DBS may provide beneficial effects on response inhibition without the detrimental effect on action selection seen with 130 Hz-DBS. FundingThis study was supported by the SUCCESS program of Philipps-University Marburg (JW), the Hessian Ministry of Sciences and the Arts, clusterproject: The Adaptive Mind - TAM (FB / AK) and the German Research Foundation (DFG). International Research Training Group 1901 (FB / AK)

neuroscience↗

bioRxiv2020

Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo

Parkinsons disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Our results show that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found doxycycline induces a cellular redistribution of the aggregates in an animal model of PD that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies.

molecular biology↗

bioRxiv2017

Reducing Pyrrolysine tRNA Copy Number Improves the Performance of Genetic Code Expansion in Live Cell Imaging of Bioorthogonally Labeled Proteins

Genetic code expansion enables the incorporation of non-canonical amino acids (ncAAs) into expressed proteins. ncAAs are usually encoded by a stop codon that is decoded by an exogenous orthogonal aminoacyl tRNA synthetase and its cognate suppressor tRNA, such as the pyrrolysine synthetase/[Formula] pair. In such systems, stop codon suppression is dependent on the intracellular levels of the exogenous tRNA. Therefore, multiple copies of the tRNAPyl gene (PylT) are encoded to improve ncAA incorporation. However, certain applications in mammalian cells, such as live-cell imaging applications, where labelled tRNA contributes to background fluorescence, can benefit from the use of less invasive minimal expression systems. Accordingly, we studied the effect of tRNAPyl on live-cell fluorescence imaging of bioorthogonally-labelled intracellular proteins. We found that in COS7 cells, a decrease in PylT copy numbers had no measurable effect on protein expression levels. Importantly, reducing PylT copy numbers improved the quality of live-cells images by enhancing the signal-to-noise ratio and reducing an immobile tRNAPyl population. This enabled us to improve live cell imaging of bioorthogonally labelled intracellular proteins, and to simultaneously label two different proteins in a cell. Our results indicate that the number of introduced PylT genes can be minimized according to the transfected cell line, incorporated ncAA, and application.

synthetic biology↗