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Updated: Jun 23, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Effects of hypernatremia on the microglia
Sachiho Fuse1, Haruki Fujisawa1, Naoya Murao1
1Department of Endocrinology, Diabetes and Metabolism, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Abstract:
Signs and symptoms of hypernatremia largely indicate central nervous system dysfunction. Acute hypernatremia can cause demyelinating lesions similar to that observed in osmotic demyelination syndrome (ODS). We have previously demonstrated that microglia accumulate in ODS lesions and minocycline protects against ODS by inhibiting microglial activation. However, the direct effect of rapid rise in the sodium concentrations on microglia is largely unknown. In addition, the effect of chronic hypernatremia on microglia also remains elusive. Here, we investigated the effects of acute (6 or 24 h) and chronic (the extracellular sodium concentration was increased gradually for at least 7 days) high sodium concentrations on microglia using the microglial cell line, BV-2. We found that both acute and chronic high sodium concentrations increase NOS2 expression and nitric oxide (NO) production. We also demonstrated that the expression of nuclear factor of activated T-cells-5 (NFAT5) is increased by high sodium concentrations. Furthermore, NFAT5 knockdown suppressed NOS2 expression and NO production. We also demonstrated that high sodium concentrations decreased intracellular Ca2+ concentration and an inhibitor of Na+/Ca2+ exchanger, NCX, suppressed a decrease in intracellular Ca2+ concentrations and NOS2 expression and NO production induced by high sodium concentrations. Furthermore, minocycline inhibited NOS2 expression and NO production induced by high sodium concentrations. These in vitro data suggest that microglial activity in response to high sodium concentrations is regulated by NFAT5 and Ca2+ efflux through NCX and is suppressed by minocycline.
Insights
High sodium levels activate microglia, increasing nitric oxide production via NFAT5 and calcium signaling. Minocycline mitigates these effects, suggesting a therapeutic target for hypernatremia-related neurological issues.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Hypernatremia, characterized by high sodium levels, often causes central nervous system dysfunction.
- Microglia are implicated in neurological damage, particularly in conditions like osmotic demyelination syndrome (ODS).
- Minocycline has shown protective effects against ODS by modulating microglial activation.
Purpose of the Study:
- To investigate the impact of acute and chronic high sodium concentrations on microglial cells.
- To elucidate the molecular mechanisms underlying microglial responses to hypernatremia.
- To assess the potential of minocycline in modulating these responses.
Main Methods:
- Utilized the BV-2 microglial cell line to study effects of acute (6-24h) and chronic (≥7 days) high sodium exposure.
- Measured nitric oxide (NO) production and NOS2 expression.
- Investigated the role of nuclear factor of activated T-cells-5 (NFAT5), intracellular calcium (Ca2+), and the Na+/Ca2+ exchanger (NCX).
Main Results:
- Both acute and chronic high sodium increased NOS2 expression and NO production in microglia.
- High sodium elevated NFAT5 expression, and NFAT5 knockdown reduced NOS2 and NO.
- High sodium decreased intracellular Ca2+; NCX inhibition and minocycline suppressed these changes and NO production.
Conclusions:
- Microglial activation in response to high sodium is mediated by NFAT5 and Ca2+ efflux via NCX.
- Minocycline inhibits microglial activation induced by high sodium concentrations.
- These findings offer insights into potential therapeutic strategies for hypernatremia-induced neurological complications.
