Human in vivo evidence of reduced astrocyte activation and neuroinflammation in patients with treatment‐resistant depression following electroconvulsive therapy

Abstract

AimThis study aimed to investigate the neuroinflammatory hypothesis of depression and the potential anti‐inflammatory effect of electroconvulsive therapy (ECT) in vivo, utilizing astrocyte‐derived extracellular vesicles (ADEVs) isolated from plasma.MethodsA total of 40 patients with treatment‐resistant depression (TRD) and 35 matched healthy controls (HCs) were recruited at baseline, and 34 TRD patients completed the post‐ECT visits. Blood samples were collected at baseline and post‐ECT. Plasma ADEVs were isolated and confirmed, and the concentrations of two astrocyte markers (glial fibrillary acidic protein (GFAP) and S100β), an EV marker cluster of differentiation (CD) 81, and nine inflammatory markers in ADEVs were measured as main analyses. Additionally, correlation analysis was conducted between clinical features and ADEV protein levels as exploratory analysis.ResultsAt baseline, the TRD group exhibited significantly higher levels of two astrocyte markers GFAP and S100β, as well as CD81 compared to the HCs. Inflammatory markers interferon (IFN)‐γ, interleukin (IL)‐1β, IL‐4, IL‐6, tumor necrosis factor (TNF)‐α, IL‐10, and IL‐17A were also significantly higher in the TRD group. After ECTs, there was a significant reduction in the levels of GFAP, S100β, and CD81, along with a significant decrease in the levels of IFN‐γ and IL‐4. Furthermore, higher levels of GFAP, S100β, CD81 and inflammatory cytokines were associated with more severe depressive symptoms and poorer cognitive function.ConclusionThis study provides direct insight supporting the astrocyte activation and neuroinflammatory hypothesis of depression using ADEVs. ECT may exert anti‐inflammatory effect through inhibition of such activation of astrocytes.This article is protected by copyright. All rights reserved.

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

“…176 Intriguingly, the beneficial outcome of depression therapies like electroconvulsive therapy 177 has also been linked to its anti-inflammatory markers of plasma astrocyte-derived EVs (ADEVs) in human study. 178 Thus, a definitive correlation exists between the EVs and the molecular abnormalities in depression. Further, the close link between EVs and depression also establishes it as a useful biomarker.…”

“…Moreover, microglia-specific knockout of GLS-1 in the mice model lowered miR-666-3p and miR-7115-3p in the released exosomes and reduced inflammation . Intriguingly, the beneficial outcome of depression therapies like electroconvulsive therapy has also been linked to its anti-inflammatory markers of plasma astrocyte-derived EVs (ADEVs) in human study . Thus, a definitive correlation exists between the EVs and the molecular abnormalities in depression.…”

Urinary Astrocyte-derived Extracellular Vesicles: A Non-invasive Tool for Capturing HumanIn VivoMolecular “Movies” of Brain

“…Similar to our previous ADEV studies 47,52 , the TEM was used to get the image of EVs. Twenty μl of the EV sample was added dropwise to 200-mesh grids and incubated at RT for 10 minutes, then the grids were negatively stained with 2% phosphotungstic acid for 3 minutes, and the remaining liquid was removed by filter paper.…”

“…Generally, in this protocol, we first concentrated the urine samples and isolated the uTEVs using ultracentrifugation (UC), followed by the isolation of uADEVs using biotin-anti-GLAST-antibody, similar to the isolation of ADEVs from plasma or serum [40][41][42][43][44][45][46][47]49 .…”

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

“…During the neuroinflammation of the telencephalon, astrocytes become activated, identifiable by specific biomarkers such as GFAP, S100β, and CD81 [49,214]. The functionality of astrocytes is intricately linked to that of microglia, with various proinflammatory and anti-inflammatory cytokines and chemokines serving as crucial mediators of their interaction.…”