Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF

Antoniou, Anna; Auderset, Loic; Kaurani, Lalit; Sebastian, Eva; Zeng, Yuzhou; Allahham, Maria; Cases-Cunillera, Silvia; Schoch, Susanne; Gruendemann, Jan; Fischer, André; Schneider, Anja

doi:10.1016/j.celrep.2023.112063

Cited by 29 publications

(30 citation statements)

References 62 publications

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“…These exosome-derived miRNAs influence a variety of processes in the recipient cells, including the modulation of microglial activity ( Veremeyko et al, 2019 ), pro-inflammatory responses ( Simeoli et al, 2017 ), gene transcription in astrocytes ( Men et al, 2019 ), and brain vascular integrity ( Xu et al, 2017 ). Most recently, it was shown that brain-derived neurotrophic factor (BDNF) promotes the sorting of miRNAs to neuronal exosomes, which enhances excitatory synapse formation in recipient neurons ( Antoniou et al, 2023 ).…”

Section: Signaling Molecules Present In Neuronal Evs and Their Functionsmentioning

confidence: 99%

“…Interestingly, ESCRT-III protein Chmp1a is specifically required for the secretion of Shh via small EVs ( Coulter et al, 2018 ). On the other hand, small EV secretion of neuronal miRNAs was shown to be dependent on ceramide ( Antoniou et al, 2023 ). These findings suggest that different cargo molecules undergo distinct exosomal sorting pathways that require specific ESCRT proteins and/or lipids in neurons.…”

Section: Neuronal Ev Secretion Mechanismsmentioning

confidence: 99%

“…Similarly, APP-and Syb2-conbtaining neuronal exosomes were also shown to undergo membrane fusion ( Laulagnier et al, 2018 ; Vilcaes et al, 2021 ). On the other hand, EVs containing miRNAs are uptaken by neurons in a dynamin-dependent manner, suggesting endocytosis-dependent mechanism ( Antoniou et al, 2023 ). Therefore, it seems neurons uptake exosomes by both endocytosis and membrane fusion mechanisms.…”

Section: Neuronal Ev Uptake Mechanismsmentioning

confidence: 99%

“…Since the first demonstration that postmitotic neurons secrete exosomes by Sadoul’s group ( Faure et al, 2006 ), significant advances have been made in neuronal EV research ( Budnik et al, 2016 ; Fowler, 2019 ). Now, neuronal exosomes are implicated in a variety of processes including neurogenesis, axon guidance, synaptogenesis, synapse elimination, neuroprotection, mRNA expression, synaptic plasticity, and inflammation ( Korkut et al, 2009 ; Escudero et al, 2014 ; Gong et al, 2016 ; Lee et al, 2018 ; Sharma et al, 2019 ; Vilcaes et al, 2021 ; Antoniou et al, 2023 ). Brain EVs are also implicated for the spread of pathogenic molecules such as amyloid β (Aβ), amyloid precursor proteins (APP), prions, tau, and α-synuclein, which a recent review extensively covered ( Delpech et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Inter-neuronal signaling mediated by small extracellular vesicles: wireless communication?

Torres¹,

Lee²

2023

Front. Mol. Neurosci.

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Conventional inter-neuronal communication conceptualizes the wired method of chemical synapses that physically connect pre-and post-synaptic neurons. In contrast, recent studies indicate that neurons also utilize synapse-independent, hence “wireless” broadcasting-type communications via small extracellular vesicles (EVs). Small EVs including exosomes are secreted vesicles released by cells and contain a variety of signaling molecules including mRNAs, miRNAs, lipids, and proteins. Small EVs are subsequently absorbed by local recipient cells via either membrane fusion or endocytic processes. Therefore, small EVs enable cells to exchange a “packet” of active biomolecules for communication purposes. It is now well established that central neurons also secrete and uptake small EVs, especially exosomes, a type of small EVs that are derived from the intraluminal vesicles of multivesicular bodies. Specific molecules carried by neuronal small EVs are shown to affect a variety of neuronal functions including axon guidance, synapse formation, synapse elimination, neuronal firing, and potentiation. Therefore, this type of volume transmission mediated by small EVs is thought to play important roles not only in activity-dependent changes in neuronal function but also in the maintenance and homeostatic control of local circuitry. In this review, we summarize recent discoveries, catalog neuronal small EV-specific biomolecules, and discuss the potential scope of small EV-mediated inter-neuronal signaling.

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Section: Signaling Molecules Present In Neuronal Evs and Their Functionsmentioning

confidence: 99%

Section: Neuronal Ev Secretion Mechanismsmentioning

confidence: 99%

Section: Neuronal Ev Uptake Mechanismsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inter-neuronal signaling mediated by small extracellular vesicles: wireless communication?

Torres¹,

Lee²

2023

Front. Mol. Neurosci.

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show abstract

“…Numerous neuronal functions, including mRNA expression, synaptic plasticity, axon guidance, neurogenesis, synapse elimination, inflammation, neuroprotection, and synaptogenesis, have been shown to be impacted by specific compounds carried by neuronal exosomes. 79,[83][84][85][86][87][88][89] Hence, it is widely believed that the transmission of exosomes, facilitating volume transmission, plays a significant role not only in the modulation of neuronal function based on activity but also in the preservation and regulation of local circuitry homeostasis. 79 Only the most recent research on the signaling function of neural and non-neuronal exosomes in the context of cancer neurology will be included in this review.…”

Section: Exosomes Mediate "Wireless Communications" Between the Nervo...mentioning

confidence: 99%

Progress in cancer neuroscience

Lan,

Zou,

Wang

et al. 2023

MedComm

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Cancer of the central nervous system (CNS) can crosstalk systemically and locally in the tumor microenvironment and has become a topic of attention for tumor initiation and advancement. Recently studied neuronal and cancer interaction fundamentally altered the knowledge about glioma and metastases, indicating how cancers invade complex neuronal networks. This review systematically discussed the interactions between neurons and cancers and elucidates new therapeutic avenues. We have overviewed the current understanding of direct or indirect communications of neuronal cells with cancer and the mechanisms associated with cancer invasion. Besides, tumor‐associated neuronal dysfunction and the influence of cancer therapies on the CNS are highlighted. Furthermore, interactions between peripheral nervous system and various cancers have also been discussed separately. Intriguingly and importantly, it cannot be ignored that exosomes could mediate the “wireless communications” between nervous system and cancer. Finally, promising future strategies targeting neuronal–brain tumor interactions were reviewed. A great deal of work remains to be done to elucidate the neuroscience of cancer, and future more research should be directed toward clarifying the precise mechanisms of cancer neuroscience, which hold enormous promise to improve outcomes for a wide range of malignancies.

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Multiomic integration reveals neuronal‐extracellular vesicle coordination of gliotic responses in degeneration

Cioanca,

Wooff,

Aggio‐Bruce

et al. 2023

J of Extracellular Vesicle

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In the central nervous system (CNS), including in the retina, neuronal‐to‐glial communication is critical for maintaining tissue homeostasis including signal transmission, transfer of trophic factors, and in the modulation of inflammation. Extracellular vesicle (EV)‐mediated transport of molecular messages to regulate these processes has been suggested as a mechanism by which bidirectional communication between neuronal and glial cells can occur. In this work we employed multiomics integration to investigate the role of EV communication pathways from neurons to glial cells within the CNS, using the mouse retina as a readily accessible representative CNS tissue. Further, using a well‐established model of degeneration, we aimed to uncover how dysregulation of homeostatic messaging between neurons and glia via EV can result in retinal and neurodegenerative diseases. EV proteomics, glia microRNA (miRNA) Open Array and small RNA sequencing, and retinal single cell sequencing were performed, with datasets integrated and analysed computationally. Results demonstrated that exogenous transfer of neuronal miRNA to glial cells was mediated by EV and occurred as a targeted response during degeneration to modulate gliotic inflammation. Taken together, our results support a model of neuronal‐to‐glial communication via EV, which could be harnessed for therapeutic targeting to slow the progression of retinal‐, and neuro‐degenerations of the CNS.

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Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF

Cited by 29 publications

References 62 publications

Inter-neuronal signaling mediated by small extracellular vesicles: wireless communication?

Inter-neuronal signaling mediated by small extracellular vesicles: wireless communication?

Progress in cancer neuroscience

Multiomic integration reveals neuronal‐extracellular vesicle coordination of gliotic responses in degeneration

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