Cell Surface Sialylation Modulates Neuronal Excitability and Network Integration

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Abstract/Contents

Abstract
Neurons are coated in a thick layer of glycoproteins and glycolipids called the glycocalyx. The neuronal glycocalyx is highly sialylated, and depletion of these surface sialosides is associated with neuroinflammatory disorders through an uncharacterized mechanism. The basic role of the glycocalyx in affecting electrical activity in neurons also remains unknown despite studies demonstrating that global desialylation leads to a reduction in action potential firing rate. This is due in part to the dual technical challenge of manipulating glycans in a subpopulation-specific manner and measuring the internal electrophysiology of several neurons simultaneously. To meet these challenges, this work aims to develop a voltage imaging platform to investigate how network activity in mouse neuron cultures change in response to linkage-specific sialoside removal. We also characterize a pathway by which activated microglia, the resident phagocytes of the brain, alter the functional connectivity of nearby neuronal networks via secretion of extracellular vesicle-bound Neuraminidase 3 (Neu3). Altogether, these results reveal that distinct subpopulations of sialosides play critical roles in network activity and uncover a new molecular mechanism by which microglia may influence neuronal electrophysiology. These discoveries present Neu3 as a potential therapeutic target for neuroinflammatory conditions and demonstrate the importance of glycosylation in neuronal communication.

Description

Type of resource text
Date created June 2021
Date modified December 5, 2022
Publication date May 5, 2022

Creators/Contributors

Author Wang, Catherine
Degree granting institution Stanford University, Department of Biology, 2021
Thesis advisor Bertozzi, Carolyn
Thesis advisor Chen, Xiaoke

Subjects

Subject Biology
Subject glycocalyx
Subject sialic acid
Subject electrophysiology
Subject microglia
Subject neuroinflammation
Subject voltage imaging
Subject Stanford ChEM-H
Genre Text
Genre Thesis

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Location https://purl.stanford.edu/fs522xc1244

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This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).

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Preferred citation
Wang CL & Bertozzi CR (2021). Cell Surface Sialylation Modulates Neuronal Excitability and Network Integration. Stanford Digital Repository. Available at: https://purl.stanford.edu/fs522xc1244

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Undergraduate Theses, Department of Biology, 2020-2021

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