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LPS-Activated Microglial Cell-Derived Conditioned Medium Protects HT22 Neuronal Cells against Glutamate-Induced
Mauricio Tavares Jacques1, Luciano Saso2, Marcelo Farina1
1Department of Biochemistry, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil.
Abstract:
Neuron-glia interactions are essential for the central nervous system's homeostasis. Microglial cells are one of the key support cells in the brain that respond to disruptions in such homeostasis. Although their participation in neuroinflammation is well known, studies investigating their role in ferroptosis, an iron-dependent form of nonapoptotic cell death, are lacking. To address this issue, we explored whether microglial (BV-2 cells) activation products can intensify, mitigate or block oxidative and/or ferroptotic damage in neuronal cells (HT22 cell line). Cultured BV-2 microglial cells were stimulated with 5-100 ng/mL lipopolysaccharide (LPS) for 24 h and, after confirmation of microglial activation, their culture medium (conditioned media; CM) was transferred to neuronal cells, which was subsequently (6 h later) exposed to glutamate or tert-butyl hydroperoxide (t-BuOOH). As a major finding, HT22 cells pretreated for 6 h with CM exhibited a significant ferroptosis-resistant phenotype characterized by decreased sensitivity to glutamate (15 mM)-induced cytotoxicity. However, no significant protective effects of LPS-activated microglial cell-derived CM were observed in t-BuOOH (30 µM)-challenged cells. In summary, activated microglia-derived molecules may protect neuronal cells against ferroptosis. The phenomenon observed in this work highlights the beneficial relationship between microglia and neurons, highlighting new possibilities for the control of ferroptosis.
Insights
Activated microglia release factors that protect neurons from ferroptosis, a form of iron-dependent cell death. This study reveals a beneficial neuron-microglia interaction, offering new avenues for ferroptosis control.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Neuron-glia interactions maintain central nervous system homeostasis.
- Microglia are key brain support cells involved in neuroinflammation.
- The role of microglia in ferroptosis, an iron-dependent cell death, is understudied.
Purpose of the Study:
- To investigate if activated microglial products affect oxidative and ferroptotic damage in neuronal cells.
- To explore the protective or detrimental effects of microglial conditioned media on neuronal ferroptosis.
Main Methods:
- BV-2 microglial cells were activated with lipopolysaccharide (LPS).
- Conditioned media (CM) from activated microglia was applied to HT22 neuronal cells.
- Neuronal cells pretreated with CM were exposed to glutamate or tert-butyl hydroperoxide (t-BuOOH).
Main Results:
- Pretreatment with activated microglial CM significantly reduced glutamate-induced ferroptosis in HT22 cells.
- Microglial CM did not show significant protective effects against t-BuOOH-induced damage.
- Activated microglia-derived molecules demonstrated a ferroptosis-resistant phenotype in neurons.
Conclusions:
- Activated microglia can produce factors that protect neurons against ferroptosis.
- This highlights a beneficial relationship between microglia and neurons.
- Findings suggest novel therapeutic strategies for controlling ferroptosis.
