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Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
Published on: May 12, 2017
Regulation of stress granule formation in human oligodendrocytes
Florian Pernin1, Qiao-Ling Cui1, Abdulshakour Mohammadnia1
1Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Abstract:
Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter. In cultures of primary human adult brain derived OLs, metabolic stress conditions induce transient SG formation in these cells. Combining pro-inflammatory cytokines, which alone do not induce SG formation, with metabolic stress results in persistence of SGs. Unlike sodium arsenite, metabolic stress induced SG formation is not blocked by the integrated stress response inhibitor. Glycolytic inhibition also induces persistent SGs indicating the dependence of SG formation and disassembly on the energetic glycolytic properties of human OLs. We conclude that SG persistence in OLs in MS reflects their response to a combination of metabolic stress and pro-inflammatory conditions.
Insights
Stress granules (SGs) form in oligodendrocytes (OLs) in multiple sclerosis (MS) lesions. Their persistence indicates a cellular response to combined metabolic and inflammatory stress in the brain.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Oligodendrocyte (OL) injury and loss are key features of multiple sclerosis (MS).
- Stress granules (SGs) are cellular structures involved in stress response, sequestering stalled mRNAs.
- The role of SGs in OLs within the context of MS pathology is not well understood.
Purpose of the Study:
- To investigate the presence and formation of stress granules (SGs) in oligodendrocytes (OLs) in multiple sclerosis (MS).
- To determine the conditions that induce SG formation and persistence in human OLs.
- To elucidate the relationship between metabolic stress, inflammation, and SG dynamics in OLs.
Main Methods:
- Immunohistochemical analysis of MS lesions and normal-appearing white matter for SG markers in OLs.
- In vitro culture of primary human adult brain-derived OLs.
- Induction of stress conditions including metabolic stress, pro-inflammatory cytokines, and glycolytic inhibition.
- Assessment of SG formation and persistence using microscopy and biochemical assays.
Main Results:
- Stress granules (SGs) were observed in oligodendrocytes (OLs) in both active and inactive MS lesions, as well as in normal-appearing white matter.
- Metabolic stress induced transient SG formation in cultured human OLs.
- Combining metabolic stress with pro-inflammatory cytokines led to persistent SGs, unlike transient SGs induced by metabolic stress alone.
- Persistent SG formation was linked to glycolytic inhibition, highlighting the dependence on cellular energetic properties.
Conclusions:
- Stress granule (SG) persistence in oligodendrocytes (OLs) in multiple sclerosis (MS) reflects a cellular response to a combination of metabolic stress and pro-inflammatory conditions.
- The findings suggest that metabolic dysregulation and inflammation contribute to SG accumulation in OLs in MS.
- Understanding SG dynamics in OLs may offer insights into MS pathogenesis and potential therapeutic targets.
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