Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; Corresponding author
Loic Auderset
Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Lalit Kaurani
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, 37075 Göttingen, Germany; Department for Systems Medicine and Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen, 37075 Göttingen, Germany
Eva Sebastian
German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Yuzhou Zeng
Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Maria Allahham
Institute of Bio- and Geosciences 1, Forschungszentrum Jülich, 52428 Jülich, Germany; Aachen Biology and Biotechnology, RWTH Aachen University, 52056 Aachen, Germany
Silvia Cases-Cunillera
Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, 53127 Bonn, Germany
Susanne Schoch
Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, 53127 Bonn, Germany
Jan Gruendemann
German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Andre Fischer
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, 37075 Göttingen, Germany; Department for Systems Medicine and Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen, 37075 Göttingen, Germany
Anja Schneider
Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Center, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; Corresponding author
Summary: Extracellular vesicles (EVs) have emerged as mediators of cellular communication, in part via the delivery of associated microRNAs (miRNAs), small non-coding RNAs that regulate gene expression. We show that brain-derived neurotrophic factor (BDNF) mediates the sorting of miR-132-5p, miR-218-5p, and miR-690 in neuron-derived EVs. BDNF-induced EVs in turn increase excitatory synapse formation in recipient hippocampal neurons, which is dependent on the inter-neuronal delivery of these miRNAs. Transcriptomic analysis further indicates the differential expression of developmental and synaptogenesis-related genes by BDNF-induced EVs, many of which are predicted targets of miR-132-5p, miR-218-5p, and miR-690. Furthermore, BDNF-induced EVs up-regulate synaptic vesicle (SV) clustering in a transmissible manner, thereby increasing synaptic transmission and synchronous neuronal activity. As BDNF and EV-miRNAs miR-218 and miR-132 were previously implicated in neuropsychiatric disorders such as anxiety and depression, our results contribute to a better understanding of disorders characterized by aberrant neural circuit connectivity.
