miRNA-loaded exosomes control neuronal morphology and synaptic transmission

Astrocytes use gliotransmitters to modulate neuronal function and plasticity. However, the role of small extracellular vesicles, called exosomes, in astrocyte-to-neuron signaling is mostly unknown. Exosomes originate in multivesicular bodies of parent cells and are secreted by fusion of the multivesicular body limiting membrane with the plasma membrane. Their molecular cargo, consisting of RNA species, proteins, and lipids, is in part cell type and cell state specific. Among the RNA species transported by exosomes, microRNAs (miRNAs) are able to modify gene expression in recipient cells. Several miRNAs present in astrocytes are regulated under pathological conditions, and this may have far-reaching consequences if they are loaded in exosomes.

Researchers from the Universidad de los Andes propose that astrocyte-derived miRNA-loaded exosomes, such as miR-26a, are dysregulated in several central nervous system diseases; thus potentially controlling neuronal morphology and synaptic transmission through validated and predicted targets. Unraveling the contribution of this new signaling mechanism to the maintenance and plasticity of neuronal networks will impact our understanding on the physiology and pathophysiology of the central nervous system.

Exosomes are released by astrocytes and their cargo internalized by neurons,
resulting in the regulation of neuronal function according to the cargo identity

exosome rna

(A) A simplified diagram of an exosome and its principal components. miR-26a is highlighted as an example of an miRNA that is highly expressed in astrocytes and transported by exosomes. (B) Targets of miR-26a in the central nervous system. miR-26a is incorporated into the RNA – induced silencing complex, where it can recognize a mRNA sequence complementary to its seed region, leading to RNA silencing. Those mRNA targets of miR-26a that have not been validated by luciferase assays are marked with an asterisk (*). Included in the diagram are targets found in silico that need further validation. Solid arrows show the reported impact on neuronal physiology. Dashed arrows show a possible impact on neuronal physiology that needs to be corroborated by experimental evidence after modulation of miR-26a levels. (C) MiR-26a targets outside the central nervous system. Their possible regulation in the brain needs to be explored experimentally.

Lafourcade C, Ramírez JP, Luarte A, Fernández A, Wyneken U. (2016) MiRNAs in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity. J Exp Neurosci 10(Suppl 1):1-9. [abstract]

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