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Updated: Jul 6, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Modulation of microglia activation by the ascorbic acid transporter SVCT2
Amanda L Marino1, Tonia S Rex2, Fiona E Harrison3
1Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, United States.
Abstract:
Neuroinflammation is a major characteristic of pathology in several neurodegenerative diseases. Microglia, the brain's resident myeloid cells, shift between activation states under neuroinflammatory conditions, both responding to, but also driving damage in the brain. Vitamin C (ascorbate) is an essential antioxidant for central nervous system function that may have a specific role in the neuroinflammatory response. Uptake of ascorbate throughout the central nervous system is facilitated by the sodium-dependent vitamin C transporter 2 (SVCT2). SVCT2 transports the reduced form of ascorbate into neurons and microglia, however the contribution of altered SVCT2 expression to the neuroinflammatory response in microglia is not well understood. In this study we demonstrate that SVCT2 expression modifies microglial response, as shown through changes in cell morphology and mRNA expression, following a mild traumatic brain injury (mTBI) in mice with decreased or increased expression of SVCT2. Results were supported by in vitro studies in an immortalized microglial cell line and in primary microglial cultures derived from SVCT2-heterozygous and transgenic animals. Overall, this work demonstrates the importance of SVCT2 and ascorbate in modulating the microglial response to mTBI and suggests a potential role for both in response to neuroinflammatory challenges.
Insights
Vitamin C transporter SVCT2 influences microglial activation in neuroinflammation. Altered SVCT2 expression modifies microglial responses to mild traumatic brain injury, highlighting its role in brain injury and neuroinflammation.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Neuroinflammation is a key factor in neurodegenerative diseases.
- Microglia, the brain's immune cells, play a dual role in neuroinflammation, both responding to and causing damage.
- Vitamin C (ascorbate) is a crucial antioxidant in the central nervous system, potentially impacting neuroinflammation.
Purpose of the Study:
- To investigate the role of sodium-dependent vitamin C transporter 2 (SVCT2) in microglial response to neuroinflammation.
- To determine how altered SVCT2 expression affects microglial activation following mild traumatic brain injury (mTBI).
Main Methods:
- Studied mice with genetically modified SVCT2 expression (decreased or increased) following mTBI.
- Utilized in vitro studies with immortalized microglial cell lines.
- Analyzed primary microglial cultures from SVCT2-heterozygous and transgenic animals.
- Assessed changes in microglial cell morphology and mRNA expression.
Main Results:
- SVCT2 expression significantly modifies microglial morphology and mRNA expression in response to mTBI.
- In vitro and in vivo studies confirmed the impact of SVCT2 levels on microglial activation.
- Demonstrated that SVCT2 influences the microglial response to brain injury.
Conclusions:
- SVCT2 and ascorbate are important modulators of the microglial response to mTBI.
- Findings suggest a potential therapeutic role for SVCT2 and ascorbate in neuroinflammatory conditions.
- Highlights the significance of vitamin C transport in brain health and injury response.
