Journal Article

DZNE-2023-00329

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF.

Antoniou, A. (First author)DZNE* ; Auderset, L.DZNE* ; Kaurani, L.DZNE* ; Sebastian, E.DZNE* ; Zeng, Y.DZNE* ; Allahham, M. ; Cases-Cunillera, S. ; Schoch, S. ; Gründemann, J.DZNE* ; Fischer, A.DZNE* ; Schneider, A. (Last author)DZNE*

2023
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2023.112063

Abstract: 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.

Keyword(s): MicroRNAs: genetics (MeSH) ; MicroRNAs: metabolism (MeSH) ; Brain-Derived Neurotrophic Factor: metabolism (MeSH) ; Neurons: metabolism (MeSH) ; Extracellular Vesicles: metabolism (MeSH) ; MicroRNAs ; BDNF ; CP: Neuroscience ; exosome ; extracellular vesicle ; microRNA ; network connectivity ; neural circuit ; synapse ; synapse clustering ; Brain-Derived Neurotrophic Factor

Note: CC BY

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Contributing Institute(s):

1. Translational Dementia Research (Bonn) (AG Schneider)
2. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
3. Neural Circuit Computations (AG Gründemann)
4. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)
3. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2023

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Database coverage:
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