Extracellular Vesicles Taken up by Astrocytes

Ogaki, Ari; Ikegaya, Yuji; Koyama, Ryuta

doi:10.3390/ijms221910553

Cited by 14 publications

(16 citation statements)

References 86 publications

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“…The absorption by astrocytes of exosomes derived from neurons, monocytes, and glial cells, as well as stem cells, has been investigated in some depth [ 62 ]. In the present study, we observed that MuVs were moderately absorbed by astrocytes.…”

Section: Discussionmentioning

confidence: 99%

The Neurotoxicity of Vesicles Secreted by ALS Patient Myotubes Is Specific to Exosome-Like and Not Larger Subtypes

Anakor

Milla

Connolly

et al. 2022

Cells

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Extracellular vesicles can mediate communication between tissues, affecting the physiological conditions of recipient cells. They are increasingly investigated in Amyotrophic Lateral Sclerosis, the most common form of Motor Neurone Disease, as transporters of misfolded proteins including SOD1, FUS, TDP43, or other neurotoxic elements, such as the dipeptide repeats resulting from C9orf72 expansions. EVs are classified based on their biogenesis and size and can be separated by differential centrifugation. They include exosomes, released by the fusion of multivesicular bodies with the plasma membrane, and ectosomes, also known as microvesicles or microparticles, resulting from budding or pinching of the plasma membrane. In the current study, EVs were obtained from the myotube cell culture medium of ALS patients or healthy controls. EVs of two different sizes, separating at 20,000 or 100,000 g, were then compared in terms of their effects on recipient motor neurons, astrocytes, and myotubes. Compared to untreated cells, the smaller, exosome-like vesicles of ALS patients reduced the survival of motor neurons by 31% and of myotubes by 18%, decreased neurite length and branching, and increased the proportion of stellate astrocytes, whereas neither those of healthy subjects, nor larger EVs of ALS or healthy subjects, had such effects.

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Section: Discussionmentioning

confidence: 99%

The Neurotoxicity of Vesicles Secreted by ALS Patient Myotubes Is Specific to Exosome-Like and Not Larger Subtypes

Anakor

Milla

Connolly

et al. 2022

Cells

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“…This result indicates a slow internalization rate in astrocytes compared to microglia, the professional phagocytes of the CNS (Figure 1, 10). Under physiological conditions, exosome uptake regulates many functions of astrocytes, such as maintenance of BBB integrity, synaptic regulation and glutamate level modulation, providing neuroprotective services to neurons (Vasile et al, 2017; Ogaki et al, 2021). Microglia achieve excitatory neurotransmission and inflammatory response through exosome circulation (Paolicelli et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Under physiological conditions, exosome uptake regulates many functions of astrocytes, such as maintenance of BBB integrity, synaptic regulation and glutamate level modulation, providing neuroprotective services to neurons (Vasile et al, 2017;Ogaki et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Microglia and astrocytes differentially endocytose exosomes facilitating alpha-Synuclein endolysosomal sorting

Pantazopoulou

Alexaki

Lamprokostopoulou

et al. 2022

Preprint

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Exosomes have emerged as key players in cell-to-cell communication in both physiological and pathological processes in the Central Nervous System (CNS). Thus far, the intracellular pathways involved in uptake and trafficking of exosomes within different cell types of the brain (microglia and astrocytes) are poorly understood. In our study, the endocytic processes and subcellular sorting of exosomes were investigated in primary glial cells, particularly linked with the exosome-associated α-synuclein (α-syn) transmission. Mouse microglia and astrocytic primary cultures were incubated with DiI-stained mouse brain-derived exosomes. The internalization and trafficking pathways were analysed in cells treated with pharmacological reagents that block the major endocytic pathways. Brain-derived exosomes were internalized by both glial cell types; however, uptake was more efficient in microglia than in astrocytes. Colocalization of exosomes with early and late endocytic markers (Rab5, Lamp1) indicated that exosomes are sorted to endolysosomes for subsequent processing. Treatment with Cytochalasin D, that blocks actin-dependent phagocytosis and/or macropinocytosis, inhibited exosome entry into glial cells, whereas treatment with inhibitors that strip off cholesterol from the plasma membrane, induced uptake, however differentially altered endosomal sorting. Exosome-associated fibrillar α-Syn was efficiently internalized and detected in Rab5- and Lamp1- positive compartments within microglia. Our study strongly suggests that exosomes enter glial cells through an actin network-dependent endocytic pathway and are sorted to endolysosomes for subsequent processing. Further, brain-derived exosomes are capable of mediating cell-to-glia transmission of pathological α-Syn that is also targeted to the endosomal pathway, suggesting a possible beneficial role in microglia-mediated clearance of toxic protein aggregates, present in numerous neurodegenerative diseases.

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“…They play a number of significant roles in different diseases and inflammation. ECVs can affect the expression of genes and proteins, as well as the manifestations of biological activities through the regulation of intercellular communications 4 . Exosomes, as shown in Figure 1, are one of the three primary types of ECVs that cells release, along with microvesicles and apoptotic bodies 5 …”

Section: Introductionmentioning

confidence: 99%

Intrinsic factors behind long‐COVID: I. Prevalence of the extracellular vesicles

El-Maradny

Rubio‐Casillas

Uversky

et al. 2023

J of Cellular Biochemistry

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It can be argued that the severity of COVID-19 has decreased in many countries. This could be a result of the broad coverage of the population by vaccination campaigns, which often reached an almost compulsory status in many places. Furthermore, significant roles were played by the multiple mutations in the body of the virus, which led to the emergence of several new SARS-CoV-2 variants with enhanced infectivity but dramatically reduced pathogenicity. However, the challenges associated with the development of various side effects and their persistence for long periods exceeding 20 months as a result of the SARS-CoV-2 infection, or taking available vaccines against it, are spreading horizontally and vertically in number and repercussions. For example, the World Health Organization announced that there are more than 17 million registered cases of long-COVID (also known as post-COVID syndrome) in the European Union countries alone. Furthermore, by using the PubMed search engine, one can find that more than 10 000 articles have been published focusing exclusively on long-COVID. In light of these enormous and ever-increasing numbers of cases and published articles, most of which are descriptive of the various long-COVID symptoms, the need to know the reasons behind this phenomenon raises several important questions. Is long-COVID caused by the continued presence of the virus or one/several of its components in the recovering individual body for long periods of time, which urges the body to respond in a way that leads to long-COVID development? Or are there some latent and limited reasons related to the recovering patients themselves? Or is it a sum of both? Many observations support a positive answer to the first question, whereas others back the second question but typically without releasing a fundamental reason/signal behind it. Whatever the answer is, it seems that the real reasons behind this widespread phenomenon remain unclear. This report opens a series of articles, in which we will try to shed light on the underlying causes that could be behind the long-COVID phenomenon.

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Extracellular Vesicles Taken up by Astrocytes

Cited by 14 publications

References 86 publications

The Neurotoxicity of Vesicles Secreted by ALS Patient Myotubes Is Specific to Exosome-Like and Not Larger Subtypes

The Neurotoxicity of Vesicles Secreted by ALS Patient Myotubes Is Specific to Exosome-Like and Not Larger Subtypes

Microglia and astrocytes differentially endocytose exosomes facilitating alpha-Synuclein endolysosomal sorting

Intrinsic factors behind long‐COVID: I. Prevalence of the extracellular vesicles

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