Neuron-derived extracellular vesicles enriched from plasma show altered size and miRNA cargo as a function of antidepressant drug response

The miRNome of Depression

“…Circulating miRNAs appear to be good candidates in biomarker research due to their high level of stability in the blood [ 89 , 90 ] and the presence of brain-specific miRNA transcripts, such as miR-9, that can be detected in body fluids [ 91 ]. Indeed, numerous scientific reports have shown that brain-specific miRNAs can effectively cross the blood–brain barrier and are detectable in blood [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ], as well as in brain-derived extracellular vesicles circulating in the bloodstream [ 93 ]. The ability of brain-specific miRNAs to pass through the blood–brain barrier makes them ideal biomarkers of brain processes, including mental illnesses such as depression.…”

“…Interestingly, it is possible to extract the extracellular vesicles of brain origin from blood, i.e., those extracellular vesicles that were released from brain cells [ 93 , 143 ]. By studying brain-derived extracellular vesicles (BDEVs), one may obtain molecular information specific to the central nervous system.…”

“…Indeed, it has been shown that the levels of miR-17-5p in neuron-derived extracellular vesicles found in blood positively correlated with intensification of symptoms of a subthreshold depressive state in humans [ 143 ]. Comprehensive molecular analysis of neuron-derived extracellular vesicles found in the plasma of depressed patients treated for 8 weeks with escitalopram demonstrated that these vesicles had brain-specific protein markers and contained miRNAs enriched for brain function [ 93 ]. The size of neuron-derived extracellular vesicles found in depressed patients was smaller than in heathy controls and this effect was reversed after antidepressant treatment [ 93 ].…”

“…Comprehensive molecular analysis of neuron-derived extracellular vesicles found in the plasma of depressed patients treated for 8 weeks with escitalopram demonstrated that these vesicles had brain-specific protein markers and contained miRNAs enriched for brain function [ 93 ]. The size of neuron-derived extracellular vesicles found in depressed patients was smaller than in heathy controls and this effect was reversed after antidepressant treatment [ 93 ]. Furthermore, time-dependent changes in miR-21-5p, miR-30d-5p and miR-486-5p levels in neuron-derived extracellular vesicles were associated with a different response of depressed patients to antidepressant therapy [ 93 ], suggesting that changes in miRNA cargo found in peripherally extracted neuron-derived extracellular vesicles may be a good noninvasive biomarker of antidepressant treatment response.…”

‘Treasure’ in garbage bags: extracellular vesicles based biomarker for neurological diseases

“…A recent elegantly designed study by Saeedi et al showed the potential of NDEVs in identifying the effect of an antidepressant drug in major depressive disorder (MDD) patients (16). Authors in that study isolated EVs from the plasma of control and MDD subjects and enriched for NDEVs using neural cell adhesion molecule L1CAM, both before (T0) and after 8 weeks of therapy (T8) with antidepressant drug escitalopram.…”