Microglia Mediate Contact-Independent Neuronal Network Remodeling via Secreted Neuraminidase-3 Associated with Extracellular Vesicles
Open accessAbstract
High Resolution Image Download MS PowerPoint Slide Neurons communicate with each other through electrochemical transmission at synapses. Microglia, the resident immune cells of the central nervous system, modulate this communication through a variety of contact-dependent and -independent means. Microglial secretion of active sialidase enzymes upon exposure to inflammatory stimuli is one unexplored mechanism of modulation. Recent work from our lab showed that treatment of neurons with bacterial sialidases disrupts neuronal network connectivity. Here, we find that activated microglia secrete neuraminidase-3 (Neu3) associated with fusogenic extracellular vesicles. Furthermore, we show that Neu3 mediates contact-independent disruption of neuronal network synchronicity through neuronal glycocalyx remodeling. We observe that NEU3 is transcriptionally upregulated upon exposure to inflammatory stimuli and that a genetic knockout of NEU3 abrogates the sialidase activity of inflammatory microglial secretions. Moreover, we demonstrate that Neu3 is associated with a subpopulation of extracellular vesicles, possibly exosomes, that are secreted by microglia upon inflammatory insult. Finally, we demonstrate that Neu3 is necessary and sufficient to both desialylate neurons and decrease neuronal network connectivity. These results implicate Neu3 in remodeling of the glycocalyx leading to aberrant network-level activity of neurons, with implications in neuroinflammatory diseases such as Parkinson’s disease and Alzheimer’s disease.
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Liposome fusion is a method to directly modify EVs.
“Liposome fusion is also a method to directly modify EVs [225].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [225]
The Results and Discussion section describes microglial EVs carrying Neu3 and EV fusion with neuronal membranes, not liposome fusion as a method for directly modifying EVs. Searches for “liposome fusion,” “EV modification,” and “liposome” found no passage addressing that method. (LLM, conf=0.76)
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- Authors
- Delaveris, C. S., Wang, C. L., Riley, N. M., Li, S., Kulkarni, R. U., & Bertozzi, C. R.
- Affiliations
- Stanford University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kulkarni, Rishikesh U.
- Bertozzi, Carolyn R.
- ORCID
- Venue
- ACS Central Science
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-10-31
- Volume
- 9
- Issue
- 11
- Pages
- 2108-2114
- ISSN
- 2374-7943 (ISSN-L)
- 2374-7951
- PMC
- PMC10683476
- OpenAlex
- W4388084096
- Cited by
- 25
- References
- 38
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 6
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- ACS Central Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Division of Graduate Education (DGE-114747)
- Stanford University
- National Institute of General Medical Sciences (GM058867, K99GM147304)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, neuraminidase, extracellular vesicles, exosomes, neuronal network connectivity, desialylation, neuroinflammation, Parkinson's disease, Alzheimer's disease
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