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Updated: May 7, 2026

Analyzing Platelet Subpopulations by Multi-color Flow Cytometry
Published on: June 10, 2025
A serotonin-induced N-glycan switch regulates platelet aggregation.
Charles P Mercado1, Maritza V Quintero, Yicong Li
1Departments of Biochemistry and Molecular Biology, and Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Elevated serotonin (5-HT) alters platelet N-glycans, switching from Neu5Ac to Neu5Gc. This change in platelet surface glycoproteins is linked to increased platelet aggregation and hypercoagulability.
Area of Science:
- Biochemistry
- Hematology
- Glycobiology
Background:
- Serotonin (5-HT) is a signaling molecule with concentration-dependent effects.
- Elevated plasma 5-HT accelerates platelet aggregation, leading to a hypercoagulable state.
- Platelet surface glycoproteins are implicated in aggregation, but their glycan content changes are not well understood.
Purpose of the Study:
- To investigate the hypothesis that elevated plasma 5-HT modifies platelet surface N-glycan content.
- To determine if altered N-glycan profiles are associated with platelet aggregation.
Main Methods:
- Mass spectrometry was used to analyze N-glycans on surface glycoproteins of platelets from wild-type mice infused with saline or 5-HT.
- Expression and catalytic activity of Cytidine monophosphate-N-acetylneuraminate hydroxylase (CMAH) were assessed in platelets.
Main Results:
- Platelets from 5-HT-infused mice showed a switch in N-glycan content from N-acetyl-neuraminic acid (Neu5Ac) to N-glycolyl-neuraminic acid (Neu5Gc).
- Increased Neu5Gc on platelet surfaces resulted from enhanced CMAH catalytic function, not expression.
- The highest Neu5Gc levels were found in platelets from 5-HT-infused, 5-HT transporter-knock out mice.
Conclusions:
- Elevated plasma 5-HT levels are linked to altered platelet N-glycan composition, specifically increased Neu5Gc.
- This N-glycan abnormality may contribute to platelet aggregation and hypercoagulability.
- Platelet 5-HT receptors might influence CMAH activity, further impacting platelet function.
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