The emerging role of exosomes in mental disorders

Saeedi, Saumeh; Israel, Sonia; Nagy, Corina; Turecki, Gustavo

doi:10.1038/s41398-019-0459-9

Cited by 311 publications

(262 citation statements)

References 98 publications

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“…Moreover, radio-and chemotherapy may also influence the development of treatment-resistant cancer cells [75], possibly through cellular reprogramming [109] and/or the formation of brain metastasis [110]. Genetics [54,111], age [71], existing comorbidities [112,113], lifestyle [114,115], and environmental [116] factors are likely to alter the extracellular fate of exosomes, which leads to CRCI (Figure 2). Changes in exosomal cargo content and their release may further influence diverse mechanisms/pathways capable of impacting the brain and CNS function, which could result in CRCI (Figure 3).…”

Section: Mechanisms Associated With Exosomes and Crcimentioning

confidence: 99%

“…Although the precise mechanisms underlying CRCI remain to be established, several studies suggest there is a link between exosomes and CRCI. Exosome biogenesis, its cargo content, function, and activity may be influenced by cancer [97], cancer therapies [93,102], genetics [54,111], age [71], existing comorbidities [112,113], lifestyle [114,115], and environmental [116] factors. Differences in exosomal content (e.g., miRNAs and proteins) and release may exert protective or damaging effects that could alter the brain and CNS function, and cause declining cognitive health in cancer survivors.…”

Section: Potential Implication Of Exosomes In Crci Researchmentioning

confidence: 99%

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Role of Exosomes in Cancer-Related Cognitive Impairment

Koh

Tan

Toh

et al. 2020

IJMS

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A decline in cognitive function following cancer treatment is one of the most commonly reported post-treatment symptoms among patients with cancer and those in remission, and include memory, processing speed, and executive function. A clear understanding of cognitive impairment as a result of cancer and its therapy can be obtained by delineating structural and functional changes using brain imaging studies and neurocognitive assessments. There is also a need to determine the underlying mechanisms and pathways that impact the brain and affect cognitive functioning in cancer survivors. Exosomes are small cell-derived vesicles formed by the inward budding of multivesicular bodies, and are released into the extracellular environment via an exocytic pathway. Growing evidence suggests that exosomes contribute to various physiological and pathological conditions, including neurological processes such as synaptic plasticity, neuronal stress response, cell-to-cell communication, and neurogenesis. In this review, we summarize the relationship between exosomes and cancer-related cognitive impairment. Unraveling exosomes' actions and effects on the microenvironment of the brain, which impacts cognitive functioning, is critical for the development of exosome-based therapeutics for cancer-related cognitive impairment.Int. J. Mol. Sci. 2020, 21, 2755 2 of 16 attention, learning, and executive function [10]. CRCI adversely affects cancer patients and survivors, causing distress and reduced quality of life, and impacts many facets of their daily lives [11]. CRCI is complicated by many factors including the direct effects of cancer, genetic predisposition (e.g., carrier of apolipoprotein E type epsilon 4 allele [12] and brain-derived neurotrophic factor Met allele [13]), comorbidities independent of the actual disease, and/or treatments or combinations of treatments administered for the disease [14].Efforts to better understand cancer-and cancer-therapy-associated cognitive impairment have relied on methods ranging from cognitive functioning assessment to imaging technologies on brain structure and function (e.g., magnetic resonance imaging scan). However, these approaches may be limited to help us understand the etiology and pathophysiology of cognitive dysfunction. The emerging application of the use of liquid biopsies (e.g., plasma and cerebrospinal fluid) as a strategy for biomarker discovery to detect, assess and monitor CRCI is fast-expanding and evolving [15,16]. In published literature, studies have revealed that genetics and neurobiological and immunological mechanisms may be involved in the biogenesis and development of CRCI. Preclinical studies have also provided insights into the pathophysiological mechanisms underlying CRCI, including neurotoxicity and inflammatory factors, which were shown to be responsible for CRCI [17]. Nevertheless, the underlying mechanisms of CRCI have yet to be established. While the role of exosomes in cancer has been well-documented [18][19][20], the role of cancer exosomes and their ability ...

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Section: Mechanisms Associated With Exosomes and Crcimentioning

confidence: 99%

Section: Potential Implication Of Exosomes In Crci Researchmentioning

confidence: 99%

Role of Exosomes in Cancer-Related Cognitive Impairment

Koh

Tan

Toh

et al. 2020

IJMS

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“…Interestingly, it has been recently shown that inflammatory stimuli are able to modify the miRNA cargo of miR-125a-5p and miR-16-5p in glial sEVs to decrease the dendritic complexity of developing hippocampal neurons [8]. New exciting and growing evidence claims for a role of exosome-like vesicles in mental disorders [80].…”

Section: Astrocyte-derived Sevs In Neurological Conditionsmentioning

confidence: 99%

Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

Luarte¹,

Henzi²,

Fernández³

et al. 2020

Preprint

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In the last decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) which are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e. GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation and also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.Here, we showed that cultured astrocytes that express GFP-tagged Aldo C (Aldo C-GFP) transfer the derived sEVs, carrying the recombinant protein, in order to develop hippocampal neurons, impacting on their dendritic complexity. Using bioinformatics combined with biochemical and molecular approaches, we postulated and then confirmed that the content of miRNA-26a-5 is regulated in Aldo C-GFP-electroporated astrocytes and their sEVs. Finally, we showed that the miRNA-26a-5p-carried by Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) actively regulate the expression of some relevant neuronal proteins for morphogenesis and dendritic complexity. Our results show that sEVs from astrocytes can regulate dendritic complexity depending on the activity of miRNA-26a-5p.. Preprints (www.preprints.org) | NOT PEER-REVIEWED |

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“…Exosomes are naturally occurring biological nanoparticles, with their size usually defined in the range from ∼30 nm up to 100 nm or sometimes up to 200 nm . Other types of extracellular vesicles (EVs) include microvesicles (50–1,000 nm, which bud directly off the plasma membrane), ectosomes (vesicles assembled at and released from a plasma membrane), shedding vesicles, microparticles and apoptotic vesicles (500–2,000 nm, which bud off the membrane of cells undergoing apoptosis) . In another paper, extracellular vesicles were divided into distinct subpopulations based on their size: 90–120 nm (large exosomes), 60–80 nm (small exosomes) and 35 nm (non‐membranous particles called exomeres) (Figure ).…”

Section: Exosomesmentioning

confidence: 99%

“…Circulating myocardial microRNAs carried by exosomes are responsible for the cross‐talk between ischemic heart and bone marrow and thereby make possible the systemic response to cardiac injury required for cardiac repair and circulating microRNAs were involved in signalling causing pre‐term birth in mice . Since exosomes can carry cargo across the blood‐brain barrier and they lack an immune response, they play an important role in the development and progression of neurodegenerative and mental diseases, as well as in neurophysiological processes . Moreover, enhanced penetration through the blood brain barrier was achieved by the coating of gold nanoparticles (NPs) by neuron‐targeted exosomes …”

Section: Exosomesmentioning

confidence: 99%

Exosomes as a Source of Cancer Biomarkers: Advances in Electrochemical Biosensing of Exosomes

et al. 2020

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Exosomes are naturally produced biological nanoparticles secreted by cells into body fluids and responsible for intercellular communication. Exosomes can also carry cargo affecting neighbouring cells and forming pre‐metastatic niches. Hence, exosomes are behind localised tumour development, progression, but also the induction of distant tumours forming metastasis. A substantially higher cellular activity of tumour cells results in the production of a greater number of exosomes than in normal, healthy cells. Therefore, the number of exosomes present in body fluids can serve as a good diagnostic biomarker in itself, besides the presence of other tumour biomarkers, which can be substantially enriched in exosomes compared to parental cells. This review comprehensively summarises the development of electrochemical biosensors for the detection of exosome levels, exosome‐derived cancer biomarkers in cell lines and serum samples for the better diagnosis of various cancer types. The review provides information on the design and analytical parameters of such biosensors. The clinical utility of the level of exosomes or exosome‐derived biomarkers is also provided.

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The emerging role of exosomes in mental disorders

Cited by 311 publications

References 98 publications

Role of Exosomes in Cancer-Related Cognitive Impairment

Role of Exosomes in Cancer-Related Cognitive Impairment

Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

Exosomes as a Source of Cancer Biomarkers: Advances in Electrochemical Biosensing of Exosomes

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