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Progressive white matter pathology in the spinal cord of transgenic mice expressing mutant (P301L) human tau.
- Source :
-
Journal of neurocytology [J Neurocytol] 2005 Dec; Vol. 34 (6), pp. 397-410. Date of Electronic Publication: 2006 Aug 10. - Publication Year :
- 2005
-
Abstract
- Transgenic mice expressing mutant (P301L) tau develop paresis, neurofibrillary tangles and neuronal loss in spinal motor neurons beginning at 4 to 6 months of age. Astrocytes and oligodendrocytes acquire filamentous tau inclusions at later ages. Here we report pathology in the spinal white matter of these animals. Progressive white matter pathology, detected as early as 2 months of age, was most marked in lateral and anterior columns, with sparing of posterior columns until late in the disease. Early changes in Luxol fast blue/periodic acid Schiff (LFB/PAS) and toluidine blue stained sections were vacuolation of myelin followed by accumulation of myelin figures within previous axonal tubes and finally influx of PAS-positive macrophages. Myelin debris and vacuoles were found in macrophages. At the ultrastructural level, myelinated axons showed extensive vacuolation of myelin sheaths formed by splitting of myelin lamellae at the intra-period line, while axons were atrophic and contained densely packed neurofilaments. Other axons were lost completely, resulting in collapse and phagocytosis of myelin sheaths. Also present were spheroids derived from swollen axons with thin myelin sheaths containing neurofilaments, tau filaments and degenerating organelles. Many oligodendrocytes had membrane-bound cytoplasmic bodies composed of tightly stacked lamellae capped by dense material. The vacuolar myelopathy in this model to some extent resembles that reported in acquired immune deficiency syndrome and vitamin B12 deficiency. The progressive axonal pathology is most consistent with a dying-back process caused by abnormal accumulation of tau in upstream neurons, while vacuolar myelinopathy may be a secondary manifestation of neuroinflammation.
- Subjects :
- Animals
Axons metabolism
Axons pathology
Axons ultrastructure
Disease Models, Animal
Disease Progression
Genetic Predisposition to Disease genetics
Humans
Macrophages metabolism
Macrophages pathology
Macrophages ultrastructure
Mice
Mice, Transgenic
Microscopy, Electron, Transmission
Mutation genetics
Myelin Sheath metabolism
Myelin Sheath pathology
Myelin Sheath ultrastructure
Myelitis genetics
Myelitis metabolism
Myelitis pathology
Neurodegenerative Diseases genetics
Neurodegenerative Diseases metabolism
Oligodendroglia metabolism
Oligodendroglia pathology
Oligodendroglia ultrastructure
Spinal Cord metabolism
Spinal Cord pathology
Spinal Cord physiopathology
Spinal Cord Diseases genetics
Spinal Cord Diseases metabolism
Vacuoles metabolism
Vacuoles pathology
Vacuoles ultrastructure
Wallerian Degeneration genetics
Wallerian Degeneration metabolism
tau Proteins genetics
Nerve Fibers, Myelinated metabolism
Nerve Fibers, Myelinated pathology
Neurodegenerative Diseases pathology
Spinal Cord Diseases pathology
Wallerian Degeneration pathology
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0300-4864
- Volume :
- 34
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of neurocytology
- Publication Type :
- Academic Journal
- Accession number :
- 16902761
- Full Text :
- https://doi.org/10.1007/s11068-006-8726-0