000282311 001__ 282311
000282311 005__ 20251117154407.0
000282311 037__ $$aDZNE-2025-01281
000282311 1001_ $$0P:(DE-2719)2812061$$aEpple, Robert$$b0$$udzne
000282311 245__ $$aThe Synaptic RNAome - identification, interactions and intercellular transfer
000282311 260__ $$c2021
000282311 300__ $$a122 p.
000282311 3367_ $$2DataCite$$aOutput Types/Dissertation
000282311 3367_ $$2ORCID$$aDISSERTATION
000282311 3367_ $$2BibTeX$$aPHDTHESIS
000282311 3367_ $$02$$2EndNote$$aThesis
000282311 3367_ $$0PUB:(DE-HGF)11$$2PUB:(DE-HGF)$$aDissertation / PhD Thesis$$bphd$$mphd$$s1763390467_17168
000282311 3367_ $$2DRIVER$$adoctoralThesis
000282311 502__ $$aDissertation, Georg-August-Universität Göttingen, 2021$$bDissertation$$cGeorg-August-Universität Göttingen$$d2021$$o2021-03-02
000282311 520__ $$aSynaptic plasticity is how neurons adapt to new stimuli and necessitates changes in synaptic weight. For these changes to be durable, local translation in neurites, and at pre- and post-synapses is required. Current methods do not capture the pool of local RNAs in its entirety and focus mainly on mRNAs. Here, I focused on wide-scale interactions between non-coding RNAs and mRNAs at hippocampal synapses; data were collected from synaptosomes and an advanced microfluidic culture system. This new method, SNIDER (SyNapse Isolation DevicE by Refined Cutting), was developed to obtain pure neuronal, neurite-localized RNAs; it works by precisely cutting the synaptic compartment of microfluidic chambers, yielding more mRNAs than synaptosome isolation. I also used SNIDER to study the effects of KCl stimulation on the local RNAome. In another experiment, synapses were locally perfused with an inhibitor of miR-9-5p, an abundant microRNA in synaptosomes that is linked to neuronal development as well as dendrite morphology. Surprisingly, after isolation of inhibited synapses with SNIDER, I found the local transcriptome to be unchanged - even though miR-9-5p inhibition produced clear effects in neuronal somata. Our findings, taken together with existing literature, suggested a glial origin of synaptic miR-9-5p. Astrocytes are highly abundant glia cells and their end feet often engulf the pre- and postsynapse to form the tri-partite synapse. To study astrocyte to neuron RNA transfer, I designed a novel method, InSUREns (Intercellularly Shipped and Uptaken RNAs Ensnared), whereby astrocytic RNAs were labeled with 4-thiouracil and neuronal ribosomes were labeled with HA-tags. By applying a double pull-down strategy, astrocytic RNAs that were transported into neurons for translation can then be identified. Astrocyte-derived extracellular vesicles (ADEV) were investigated as the means of RNA transportation. Indeed, ADEV internalization took place over the whole neuronal cell body, including neurites. ADEVs furthermore contained many RNAs that where identified via InSUREns. Additionally, many lncRNAs were present in ADEVs that are known to interact with synaptic RNAs. These data suggest an important role of ADEVs in supplying neuronal and synaptic RNAs. Finally, a hypothesis is developed, how astrocytic RNAs could form the synaptic tag in the synaptic tagging and capturing model.
000282311 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000282311 8564_ $$uhttp://dx.doi.org/10.53846/goediss-8506
000282311 8564_ $$uhttps://pub.dzne.de/record/282311/files/DZNE-2025-01281.pdf$$yRestricted
000282311 8564_ $$uhttps://pub.dzne.de/record/282311/files/DZNE-2025-01281.pdf?subformat=pdfa$$xpdfa$$yRestricted
000282311 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812061$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000282311 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000282311 9201_ $$0I:(DE-2719)1410002$$kAG Fischer$$lEpigenetics and Systems Medicine in Neurodegenerative Diseases$$x0
000282311 980__ $$aphd
000282311 980__ $$aEDITORS
000282311 980__ $$aVDBINPRINT
000282311 980__ $$aI:(DE-2719)1410002
000282311 980__ $$aUNRESTRICTED