Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks

Agnati, Luigi F.; Fuxé, Kjell

doi:10.1098/rstb.2013.0505

Cited by 65 publications

(71 citation statements)

References 110 publications

(219 reference statements)

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“…(ii) Extracellular vesicle-mediated volume transmission signals Studies on cultured cortical nerve cells demonstrate that extracellular membrane vesicles (EMVs) can be released from nerve cells [45], and exosomes were proposed to be a new way of interneuronal communication [19,[46][47][48]. In EMV fractions from the above cultures, GluR2 subunits of the AMPA receptors were found together inter alia with cell adhesion molecule L1 (LICAM).…”

Section: (B) Soma Level (I) Soluble Volume Transmission Signalsmentioning

confidence: 99%

“…The exosomes can move via different patterns of cell adhesion molecules and phosphatidylserine to target other neuron -glia networks. The exosomes can be internalized and then release their cargo inside target cells to transiently modify the neurochemical phenotype of the target cell [19]. The exosomes mainly originate from endosomes and are produced when multivesicular bodies are formed.…”

Section: Comparison Between Soluble and Extracellular Vesicle-mediatementioning

confidence: 99%

“…In this review, we will characterize the heterogeneities of VT including the contribution of soluble VT signals and VT signals carried by extracellular vesicles (ECVs) [19], building on the pioneering work of Simons & Raposo [20]. Furthermore, the impact of VT in the trophic units of the grey matter built up of neurons, glial cells (astroglia, microglia), blood vessels with endothelial cells and pericytes, and extracellular matrix of the CNS [21,22] will be discussed.…”

Section: Introductionmentioning

confidence: 99%

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The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

Borroto-Escuela

Agnati

Bechter

et al. 2015

Phil. Trans. R. Soc. B

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One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'. Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (point-to-point communication, the prototype being synaptic transmission with axons and terminals) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid (CSF)) involving large numbers of cells in the CNS. Volume and synaptic transmission become integrated inter alia through the ability of their chemical signals to activate different types of receptor protomers in heteroreceptor complexes located synaptically or extrasynaptically in the plasma membrane. The demonstration of extracellular dopamine (DA) and serotonin (5-HT) fluorescence around the DA and 5-HT nerve cell bodies with the Falck-Hillarp formaldehyde fluorescence method after treatment with amphetamine and chlorimipramine, respectively, gave the first indications of the existence of VT in the brain, at least at the soma level. There exist different forms of VT. Early studies on VT only involved spread including diffusion and flow of soluble biological signals, especially transmitters and modulators, a communication called extrasynaptic (short distance) and long distance (paraaxonal and paravascular and CSF pathways) VT. Also, the extracellular vesicle type of VT was demonstrated. The exosomes (endosome-derived vesicles) appear to be the major vesicular carriers for VT but the larger microvesicles also participate. Both mainly originate at the soma-dendritic level. They can transfer lipids and proteins, including receptors, Rab GTPases, tetraspanins, cholesterol, sphingolipids and ceramide. Within them there are also subsets of mRNAs and non-coding regulatory microRNAs. At the soma-dendritic membrane, sets of dynamic postsynaptic heteroreceptor complexes (built up of different types of physically interacting receptors and proteins) involving inter alia G protein-coupled receptors including autoreceptors, ion channel receptors and receptor tyrosine kinases are hypothesized to be the molecular basis for learning and memory. At nerve terminals, the presynaptic heteroreceptor complexes are postulated to undergo plastic changes to maintain the pattern of multiple transmitter release reflecting the firing pattern to be learned by the heteroreceptor complexes in the postsynaptic membrane.

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Section: (B) Soma Level (I) Soluble Volume Transmission Signalsmentioning

confidence: 99%

Section: Comparison Between Soluble and Extracellular Vesicle-mediatementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks

Borroto-Escuela

Agnati

Bechter

et al. 2015

Phil. Trans. R. Soc. B

Self Cite

110

123

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show abstract

“…Furthermore, unconventional mechanisms of membrane translocation have been discovered for FGF-2 [62], which could also apply to its release from astrocytes. Finally, neuron-glia interactions have also been shown to involve the exchange of exosomes, shed from the membranes of donor cells and then internalized by the acceptor cells [63,64].…”

Section: (B) Mechanisms Of Protein Secretion From Glial Cellsmentioning

confidence: 99%

Regulation of neuronal excitability by release of proteins from glial cells

Igelhorst

Niederkinkhaus

Karus

et al. 2015

Phil. Trans. R. Soc. B

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Effects of glial cells on electrical isolation and shaping of synaptic transmission between neurons have been extensively studied. Here we present evidence that the release of proteins from astrocytes as well as microglia may regulate voltage-activated Na þ currents in neurons, thereby increasing excitability and speed of transmission in neurons kept at distance from each other by specialized glial cells. As a first example, we show that basic fibroblast growth factor and neurotrophin-3, which are released from astrocytes by exposure to thyroid hormone, influence each other to enhance Na þ current density in cultured hippocampal neurons. As a second example, we show that the presence of microglia in hippocampal cultures can upregulate Na þ current density. The effect can be boosted by lipopolysaccharides, bacterial membrane-derived stimulators of microglial activation. Comparable effects are induced by the exposure of neuron-enriched hippocampal cultures to tumour necrosis factor-a, which is released from stimulated microglia. Taken together, our findings suggest that release of proteins from various types of glial cells can alter neuronal excitability over a time course of several days. This explains changes in neuronal excitability occurring in states of thyroid hormone imbalance and possibly also in seizures triggered by infectious diseases.

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“…-the role of exosomes as causative factors and diagnostic tools in traumatic brain injury [8]; -the differential role of microvesicles, exosomes and tunnelling microtubules in interneuronal communication [9];…”

mentioning

confidence: 99%