Neuronal Exosomal miRNA-dependent Translational Regulation of Astroglial Glutamate Transporter GLT1

Abstract

Background: Pathways involved in neuron-dependent GLT1 regulation in astrocytes remain to be characterized. Results: Neuronal microRNA 124a can be transferred into astrocytes through neuronal exosomes and significantly increases GLT1 protein expression in an indirect manner. Conclusion: Neuronal exosomal miRNA 124a is able to regulate astroglial GLT1 expression. Significance: We characterize a novel pathway in neuron-to-astrocyte communication and identify a microRNA that modulates GLT1 protein expression.

Exosomes in stroke pathogenesis and therapy

“…Intravenous administration of MSC-derived exosomes to rats subjected to focal cerebral ischemia or TBI substantially improved neurological function by promoting neurovascular remodeling during stroke and TBI recovery (116, 117, 119). Subsequently, the therapeutic ing astrocyte function (89). AMPA receptors and MAP1b are key regulators of synaptic and dendritic plasticity and axonal spouting (86,87,90).…”

“…AMPA receptors and MAP1b are key regulators of synaptic and dendritic plasticity and axonal spouting (86,87,90). The astrocyte glutamate transporter GLT-1 in rodent regulates extracellular glutamate levels and modulates synaptic activation (89). Activation of AMPA receptors contributes to motor function recovery after stroke (91).…”

Extracellular microRNAs as messengers in the central and peripheral nervous system

“…A variety of different vesicles are actively secreted from cells. MicroRNAs have been detected in exosomes [9,31,[36][37][38][39][42][43][44], shedding vesicles [32] and large dense-core vesicles (LDCVs) [45]. Proteins that have been found associated with…”

“…The increased stability of extracellular microRNAs is due to the fact that they are protected from degradation by being packaged into extracellular vesicles (EVs) [9,31,32,[36][37][38][39][42][43][44][45] or bound to proteins [46][47][48][49][50] (Figure 1). A variety of different vesicles are actively secreted from cells.…”

“…They are actively secreted by healthy cells, including cells of the nervous system [31][32][33][34][35], and can be taken up by neighbouring cells or even other tissues, where they are functionally active [31,[36][37][38][39][40][41]. Hence, extracellular microRNAs have the potential to act as messengers over both short and long distances [9][10][11].…”