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Updated: Aug 15, 2026
Selective Depletion of Microglia from Cerebellar Granule Cell Cultures Using L-leucine Methyl Ester
Published on: July 7, 2015
[Microglial cell death induced by polyamines]
Katsura Takano1, Yoichi Nakamura, Yukio Yoneda
1Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kakuma-machi, Kanazawa, 920-1192 Japan.
Abstract:
Pathological activation of microglia, which quiescently reside in physiological CNS, causes various neurodegenerative diseases. Endogenous polyamines, spermidine (SPD) and spermine (SPM) are known to be activators of cell proliferation and differentiation. We examined the effect of polyamines on microglial activation in culture. Cultured microglia prepared from the whole brains of newborn rats produced nitric oxide (NO) by the stimulation with lipopolysaccharide (LPS). LPS-induced NO production was remarkably inhibited by SPD and SPM. Cell viability assessed by total mitochondrial activity decreased by the incubation with SPD and SPM for 24 h. In astrocyte culture, on the other hand, polyamines showed no significant effect on either LPS-induced NO production or cell viability. After the treatment with SPM for 24 h, the cells changed into small round shapes, and were markedly stained with propidium iodide. By the staining with Hoechst33342, condensation and fragmentation of the nucleus were often observed. Semiquantitative analysis of fragmented DNA with the ELISA technique revealed that a large amount of fragmented DNA appeared in cytosol prior to disruption of the cell membrane, suggesting that polyamines induced apoptosis. Fragmented DNA in cytosol increased dose dependently with SPM. These results suggest that particular polyamines induce cell death through apoptosis at low concentrations in cultured microglia
Insights
Polyamines like spermidine and spermine inhibit microglial activation and nitric oxide production. These compounds also induce apoptosis, or programmed cell death, in microglia at low concentrations.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Context:
- Microglia, the immune cells of the central nervous system (CNS), play a critical role in neuroinflammation and neurodegenerative diseases when pathologically activated.
- Endogenous polyamines, such as spermidine (SPD) and spermine (SPM), are known regulators of cell proliferation and differentiation.
Purpose:
- To investigate the effects of polyamines (SPD and SPM) on microglial activation and viability in vitro.
- To determine if polyamines influence lipopolysaccharide (LPS)-induced nitric oxide (NO) production in cultured microglia.
Summary:
- Cultured rat microglia produced nitric oxide (NO) upon stimulation with lipopolysaccharide (LPS).
- Both SPD and SPM significantly inhibited LPS-induced NO production in microglia.
- Polyamines reduced microglial viability and induced apoptosis, characterized by nuclear condensation, DNA fragmentation, and cell membrane disruption, in a dose-dependent manner.
- Polyamines did not significantly affect NO production or viability in cultured astrocytes.
Impact:
- These findings suggest that specific polyamines can induce programmed cell death (apoptosis) in microglia at low concentrations.
- This study provides insights into the complex role of polyamines in neuroinflammation and potential therapeutic strategies for neurodegenerative diseases targeting microglial activation.
