Exercise-induced microRNA modulations and their role in cognition
Dissertation
Datum der mündl. Prüfung:2022-10-04
Erschienen:2022-09-27
Betreuer:Prof. Dr. André Fischer
Gutachter:Prof. Dr. André Fischer
Gutachter:Prof. Dr. Tiago Fleming Outeiro
Dateien
Name:Dissertation_Goldberg.pdf
Size:7.42Mb
Format:PDF
Zusammenfassung
Englisch
The number of people suffering from dementia is constantly increasing leading to massive long-term economic and social consequences. A healthy lifestyle and physical exercise in particular are well known for their positive effects on brain functions. Epigenetics has great potential to provide us with answers on how benefits from physical exercise can be applied to cognitively impaired elderly patients and reverse age-related and disease-associated loss of normal cognitive function. MicroRNA is a novel tool to manipulate a wide range of physiological processes as single microRNA regulates the functions of multiple genes. We found two microRNAs that were upregulated in human blood as well as in stimulated mouse muscle cells and mouse brain after physical exercise, and we validated their role in neuronal plasticity. Inhibition of microRNA-409-5p and microRNA-501-3p negatively alters neuronal morphology and electrophysiological activity in mouse wild type hippocampal neurons. Moreover, expression of microRNA-409-5p was found to be decreased in patients with genetic frontotemporal dementia. Transplantation of media from electrically stimulated muscle may alter neuronal morphology. Overexpression of microRNA-409-5p and microRNA-501-3p increases spine number but does not have an effect on mature synapse number or action potentials of wild type healthy hippocampal neurons. Further studies are needed to validate experimentally other microRNAs from the identified cluster.
Keywords: Epigenetics; MicroRNA; Neurodegeneration; Molecular neuroscience; Cognition; Exercise
Schlagwörter: MicroRNome; Transcriptome; MicroRNA modulation; Neuropsychology; Behavioural experiments; Neuronal plasticity