Paclitaxel (Taxol) attenuates clinical disease in a spontaneously demyelinating transgenic mouse and induces remyelination

Autor: Mario A. Moscarello, Samuel K. Ludwin, B Mak, Fabrizio G. Mastronardi, T A Nguyen, D. D. Wood
Rok vydání: 2002
Předmět:
Pathology
medicine.medical_specialty
Multiple Sclerosis
Paclitaxel
Drug Evaluation
Preclinical
Alpha (ethology)
Mice
Transgenic
Nerve Tissue Proteins
Nervous System Autoimmune Disease
Experimental
Mice
Mice
Neurologic Mutants
03 medical and health sciences
Myelin
0302 clinical medicine
Cerebellum
Glial Fibrillary Acidic Protein
medicine
Animals
Gliosis
030212 general & internal medicine
Remyelination
Sonic hedgehog
Myelin Proteolipid Protein
Myelin Sheath
Cell Nucleus
biology
business.industry
Multiple sclerosis
Brain
medicine.disease
Oligodendrocyte
Astrogliosis
Hereditary Central Nervous System Demyelinating Diseases
Oligodendroglia
medicine.anatomical_structure
Gene Expression Regulation
Neurology
Astrocytes
Immunology
biology.protein
Neurology (clinical)
business
Biomarkers
Cell Division
Injections
Intraperitoneal
Myelin Proteins
030217 neurology & neurosurgery
Signal Transduction
Astrocyte
Zdroj: Multiple Sclerosis Journal. 8:130-138
ISSN: 1477-0970
1352-4585
DOI: 10.1191/1352458502ms776oa
Popis: Treatment with paclitaxel by four intraperitoneal injections (20 mg/kg) 1 week apart attenuated clinical signs in a spontaneously demyelinating model, if given with onset of clinical signs. If given at 2 months of age (1 month prior to clinical signs), disease was almost completely prevented. The astrogliosis, prominent in our model, was reversed by paclitaxel as determined by astrocyte counts and quantitation of GFAP. Electron microscopic examination of affected regions at 2.5 months demonstrated that the myelin was generally normal. By 4 months of age, demyelination was common in the superior cerebellar peduncle, maximal at 6 months, but continued to 8 months. In addition to myelin vacuolation and nude axons, the presence of many thin myelin sheaths suggested remyelination or partial demyelination. Although no evidence of oligodendrocyte loss was seen, nuclear changes were observed. To substantiate that remyelination was occurring, we measured MBP (18.5 kDa), MBP-exon II, Golli-MBP, TP8, Golli-MBP-J37, platelet-derived growth factor a (PDGFRa) and sonic hedgehog (SHH). Of these TP8, PDGFRa and SHH were up-regulated in the untreated transgenic. After paclitaxel treatment, MBP-Exon II, TP8, PDGFRa and SHH were further up-regulated. We concluded that some of the effects of paclitaxel were to stimulate proteins involved in early myelinating events possibly via a signal transduction mechanism.
Databáze: OpenAIRE
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