Plasma exosomes from depression ameliorate inflammation-induced depressive-like behaviors via sigma-1 receptor delivery

Wang, Yun; Gao, Ce; Gao, Tianyu; Zhao, Lu; Zhu, Shenglong; Guo, Lin

doi:10.1016/j.bbi.2021.02.004

Cited by 39 publications

(30 citation statements)

References 34 publications

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“…Exosomes are thought to be able to change the behavior of recipient cells and act as key players in many cellular and molecular pathways in mental disorders [7,8]. Plasma exosomes can deliver sigma-1 receptors to the central nervous system, ameliorate inflammation, and improve depressive-like behavior in animals [9]. The differential expression of microRNAs in the exosomes of the rat model was associated with the MAPK pathway, Wnt pathway, and mTOR pathway [10].…”

Section: Introductionmentioning

confidence: 99%

Exosomal let-7e, miR-21-5p, miR-145, miR-146a and miR-155 in Predicting Antidepressants Response in Patients with Major Depressive Disorder

et al. 2021

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The intracellular microRNAs that negatively regulate Toll-like receptor 4 signaling pathways in peripheral blood mononuclear cells are associated with major depressive disorder (MDD). However, that the distribution of these microRNAs in exosomes could be a biomarker of central nervous system diseases is just beginning to be explored. In the present study, we isolated serum exosomes from patients with MDD and healthy controls to explore the levels of exosomal microRNAs, including let-7e, miR-21-5p, miR-223, miR-145, miR-146a, and miR-155. We also investigated the changes of these exosomal microRNAs after antidepressant treatment and their association with clinical changes in scores on the Hamilton Depression Rating Scale. An ANCOVA adjusted by age, sex, BMI, and smoking showed higher expression levels of miR-146a (p = 0.006) in patients with MDD compared to controls. Patients who achieved remission showed significantly lower let-7e, miR-21-5p, miR-145, miR-146a, and miR-155 levels before treatment and increased levels after antidepressant treatment compared with the non-remission group. Through receiver operating characteristic (ROC) analysis, let-7e, miR-145, and miR-146a showed acceptable discrimination between the remission and non-remission groups, whereas miR-21-5p and miR-155 showed poor discrimination. These findings demonstrate that exosomal microRNAs may play essential roles in predicting antidepressants response.

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Section: Introductionmentioning

confidence: 99%

Exosomal let-7e, miR-21-5p, miR-145, miR-146a and miR-155 in Predicting Antidepressants Response in Patients with Major Depressive Disorder

et al. 2021

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“…Moss L et al found that intranasal exosomes inhibit microglial activation (Moss et al, 2021 ). Plasma exosomes inhibit LPS-induced microglial inflammatory response (Wang et al, 2021 ). Bone marrow mesenchymal stem cell-derived exosomes alleviate neuroinflammation by modulating microglial activation (Liu et al, 2021b ).…”

Section: Discussionmentioning

confidence: 99%

Exercise Intervention Modulates Synaptic Plasticity by Inhibiting Excessive Microglial Activation via Exosomes

Liu³

et al. 2022

Front. Cell. Neurosci.

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BackgroundExosomes can activate microglia to modulate neural activity and synaptic plasticity by phagocytosis of neural spines or synapses. Our previous research found that an early 4-week exercise intervention in middle cerebral artery occlusion (MCAO) rats can promote the release of exosomes and protect the brain. This study intended to further explore the intrinsic mechanism of neuroprotection by exosome release after exercise.MethodsRats were randomly divided into four groups: the sham operation (SHAM), middle cerebral artery occlusion (MCAO) with sedentary intervention (SED-MCAO), MCAO with exercise intervention (EX-MCAO), and MCAO with exercise intervention and exosome injection (EX-MCAO-EXO). Modified neurological severity score (mNSS), cerebral infarction volume ratio, microglial activation, dendritic complexity, and expression of synaptophysin (Syn) and postsynaptic density protein 95 (PSD-95) were detected after 28 days of intervention.Results(1) The exercise improved body weight and mNSS score, and the survival state of the rats after exosome infusion was better. (2) Compared with the SED-MCAO group, the EX-MCAO (P = 0.039) and EX-MCAO-EXO groups (P = 0.002) had significantly lower cerebral infarct volume ratios (P < 0.05), among which the EX-MCAO-EXO group had the lowest (P = 0.031). (3) Compared with the SED-MCAO group, the EX-MCAO and EX-MCAO-EXO groups had a significantly decreased number of microglia (P < 0.001) and significantly increased process length/cell (P < 0.01) and end point/cell (P < 0.01) values, with the EX-MCAO-EXO group having the lowest number of microglia (P = 0.036) and most significantly increased end point/cell value (P = 0.027). (4) Compared with the SED-MCAO group, the total number of intersections and branches of the apical and basal dendrites in the EX-MCAO and EX-MCAO-EXO groups was increased significantly (P < 0.05), and the increase was more significant in the EX-MCAO-EXO group (P < 0.05). (5) The expression levels of Syn and PSD-95 in the EX-MCAO (PSyn = 0.043, PPSD−95 = 0.047) and EX-MCAO-EXO groups were significantly higher than those in the SED-MCAO group (P < 0.05), and the expression levels in the EX-MCAO-EXO group were significantly higher than those in the EX-MCAO group (P < 0.05).ConclusionEarly exercise intervention after stroke can inhibit the excessive activation of microglia and regulate synaptic plasticity by exosome release.

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“…A recent study shed new light on the role of sigma-1 receptors in depression. Plasma exosomes from depressed mice ameliorated depressive-like behaviors, deficiency of BDNF expression, and neuroinflammation in LPS-treated mice via sigma-1 receptor delivery ( Wang et al, 2021a , b ). The exosomes without sigma-1 receptors no longer showed the antidepressant-like effect, suggesting that sigma-1 receptors are crucial for antidepressant-like activity.…”

Section: Depressive-like State and Sigma-1 Receptorsmentioning

confidence: 99%

“…Its neuroprotective mechanism may depend on sigma-1 receptor-mediated changes like inhibition of NMDA-induced nitric oxide synthase hyperactivity, reduction of nitric oxide production ( Kurata et al, 2004 ), stimulation of phosphoinositide 3-kinase (PI3) activity ( Raval et al, 2003 ), and antiapoptotic Bcl-2 proteins ( Charalampopoulos et al, 2004 ), or upregulation of glutamate transporter-1 (GLT-1) ( Sokabe et al, 2007 ) and extracellular signal-regulated kinase (ERK) phosphorylation ( Shi et al, 2021 ). Interestingly, the optimal time window for the administration of sigma-1 receptor ligands is crucial for retinal neuroprotection – (+)-pentazocine given since post-natal day 14 (P14), but not P18, P21 or P24, to the Pde6βrd10/J (rd10) mice (mouse model of retinitis pigmentosa) preserved the visual acuity ( Wang et al, 2021a , b ). This neuroprotective mechanism of sigma-1 receptors may depend on modulation of miR-214-3p in retina, a microRNA involved in the oxidative stress ( Wang and Smith, 2019 ).…”

Section: Basic Information On Sigma-1 Receptormentioning

confidence: 99%

Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders

Sałaciak

Pytka

2022

Neuroscience & Biobehavioral Reviews

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Plasma exosomes from depression ameliorate inflammation-induced depressive-like behaviors via sigma-1 receptor delivery

Cited by 39 publications

References 34 publications

Exosomal let-7e, miR-21-5p, miR-145, miR-146a and miR-155 in Predicting Antidepressants Response in Patients with Major Depressive Disorder

Exosomal let-7e, miR-21-5p, miR-145, miR-146a and miR-155 in Predicting Antidepressants Response in Patients with Major Depressive Disorder

Exercise Intervention Modulates Synaptic Plasticity by Inhibiting Excessive Microglial Activation via Exosomes

Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders

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