TY  - JOUR
AU  - Antoniou, Anna
AU  - Auderset, Loic
AU  - Kaurani, Lalit
AU  - Sebastian, Eva
AU  - Zeng, Yuzhou
AU  - Allahham, Maria
AU  - Cases-Cunillera, Silvia
AU  - Schoch, Susanne
AU  - Gründemann, Jan
AU  - Fischer, Andre
AU  - Schneider, Anja
TI  - Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF.
JO  - Cell reports
VL  - 42
IS  - 2
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2023-00329
SP  - 112063
PY  - 2023
N1  - CC BY
AB  - 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.
KW  - MicroRNAs: genetics
KW  - MicroRNAs: metabolism
KW  - Brain-Derived Neurotrophic Factor: metabolism
KW  - Neurons: metabolism
KW  - Extracellular Vesicles: metabolism
KW  - MicroRNAs (NLM Chemicals)
KW  - BDNF (Other)
KW  - CP: Neuroscience (Other)
KW  - exosome (Other)
KW  - extracellular vesicle (Other)
KW  - microRNA (Other)
KW  - network connectivity (Other)
KW  - neural circuit (Other)
KW  - synapse (Other)
KW  - synapse clustering (Other)
KW  - Brain-Derived Neurotrophic Factor (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36753414
DO  - DOI:10.1016/j.celrep.2023.112063
UR  - https://pub.dzne.de/record/256467
ER  -