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Case report: DNA fragmentation in glial cells in a cerebral biopsy from a multiple sclerosis patient
N Benjelloun1, A Ménard, C Charriaut-Marlangue
1INSERM, Laboratoire de Neuromodulations Interactives et Neuropathologies, Paris, France.
Abstract:
Multiple sclerosis is characterized by myelin destruction and oligodendrocyte loss. The neuropathological hallmark of the disease is the presence of demyelinated plaques in the central nervous system. We have recently found a gliotoxic factor in MS cerebrospinal fluid which induces programmed cell death in vitro, in glial cells. Here we show DNA fragmentation and glial cell death in biopsy samples, obtained from a patient who underwent surgery with suspicion of tumor, and whose disease record, including brain autopsy, demonstrated an active multiple sclerosis. We used the in situ TUNEL technique, a method which sensitively detects the DNA fragmentation accompanying programmed cell death in tissue sections, and compatible with classical fixation techniques. We found intense DNA fragmentation in nuclei of glial cells at-or very near-to the site of demyelination. A double labeling technique showed that glial fibrillary associated protein positive astrocytes may undergo programmed cell death in multiple sclerosis.
Insights
Multiple sclerosis involves myelin destruction. This study found DNA fragmentation and glial cell death near demyelination sites in active multiple sclerosis patients, indicating programmed cell death contributes to the disease.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Multiple sclerosis (MS) is a central nervous system disease characterized by myelin destruction and oligodendrocyte loss.
- Demyelinated plaques are the neuropathological hallmark of MS.
- A previously identified gliotoxic factor in MS cerebrospinal fluid induces programmed cell death in glial cells in vitro.
Observation:
- This study investigated glial cell death and DNA fragmentation in brain biopsy samples from an active multiple sclerosis patient.
- The in situ TUNEL technique was employed to detect DNA fragmentation, a marker of programmed cell death, in tissue sections.
- The technique is compatible with classical fixation methods used in neuropathology.
Findings:
- Intense DNA fragmentation was observed in glial cell nuclei located at or very near demyelinated plaques.
- A double labeling technique revealed that glial fibrillary associated protein (GFAP)-positive astrocytes undergo programmed cell death in MS.
- These findings provide in vivo evidence of glial cell death in active MS lesions.
Implications:
- Programmed cell death of glial cells, including astrocytes, may play a significant role in the pathogenesis of multiple sclerosis.
- Understanding the mechanisms of glial cell death could lead to novel therapeutic strategies targeting MS.
- Further research is warranted to elucidate the specific gliotoxic factors and pathways involved in MS-induced glial cell death.