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Updated: Aug 19, 2026
An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
Published on: February 5, 2015
Modifications of oligodendroglial cells in spongiform encephalopathies
K H El Hachimi1, M P Chaunu, P Brown
1Ecole Pratique des Hautes Etudes and U. 106 INSERM, Hôpital de la Salpêtrière, Paris, France.
Abstract:
Although gray matter lesions involving neurones and astrocytes are prominent in human transmissible spongiform encephalopathies (TSE), white matter lesions have also been occasionally observed. Secondary (Wallerian) degeneration and direct myelin damage have been invoked, but the physiopathology of white matter involvement is still debated. We performed an immunohistochemistry study with anti-PrP antibodies of autopsy material of four patients with Creutzfeldt-Jakob disease (CJD), together with transmission electron microscopy (TEM) studies of conventionally processed biopsy specimens of the same patients. Light microscopy immunolabeling was observed as arrays adjacent to myelinic fibers and as a clumps adjacent to oligodendroglial nuclei; both cerebrum and cerebellum were involved. At the ultrastructural level, two types of intracellular inclusions were seen in the white matter. They were associated with dense lysosomes in oligodendroglial perikarya and in their processes. The inclusions were made of finely fibrillar, paracrystalline, amorphous, or densely osmophilic material. Thus, our findings may suggest that white matter involvement in spongiform encephalopathy is due to direct modifications of oligodendroglial cell associated with abnormal metabolism of PrP.
Insights
This study reveals that white matter damage in Creutzfeldt-Jakob disease (CJD) involves direct changes to oligodendrocytes and abnormal prion protein (PrP) metabolism, challenging previous theories on transmissible spongiform encephalopathies (TSEs).
Area of Science:
- Neuroscience
- Neuropathology
- Prion Disease Research
Background:
- Transmissible spongiform encephalopathies (TSEs), like Creutzfeldt-Jakob disease (CJD), primarily affect gray matter, but white matter lesions are occasionally observed.
- The exact mechanisms behind white matter pathology in TSEs, including potential Wallerian degeneration or direct myelin damage, remain debated.
Purpose of the Study:
- To investigate the physiopathology of white matter involvement in human Creutzfeldt-Jakob disease (CJD).
- To elucidate the role of oligodendrocytes and prion protein (PrP) in white matter lesions observed in CJD patients.
Main Methods:
- Immunohistochemistry using anti-PrP antibodies on autopsy brain tissue from four CJD patients.
- Transmission electron microscopy (TEM) on biopsy specimens from the same CJD patients.
Main Results:
- Light microscopy revealed PrP immunolabeling adjacent to myelinic fibers and oligodendroglial nuclei in both cerebrum and cerebellum.
- Ultrastructural analysis identified two types of intracellular inclusions within oligodendrocytes and their processes in white matter.
- These inclusions were associated with dense lysosomes and composed of fibrillar, paracrystalline, amorphous, or osmophilic material.
Conclusions:
- White matter involvement in CJD appears to stem from direct modifications of oligodendroglial cells.
- Abnormal metabolism of the prion protein (PrP) is likely implicated in the observed white matter pathology.
- Findings suggest a direct pathogenic role for oligodendrocytes in TSE white matter lesions, distinct from secondary degeneration.
