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@PHDTHESIS{Epple:282311,
      author       = {Epple, Robert},
      title        = {{T}he {S}ynaptic {RNA}ome - identification, interactions
                      and intercellular transfer},
      school       = {Georg-August-Universität Göttingen},
      type         = {Dissertation},
      reportid     = {DZNE-2025-01281},
      pages        = {122 p.},
      year         = {2021},
      note         = {Dissertation, Georg-August-Universität Göttingen, 2021},
      abstract     = {Synaptic 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.},
      cin          = {AG Fischer},
      cid          = {I:(DE-2719)1410002},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)11},
      url          = {https://pub.dzne.de/record/282311},
}