Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-1-22
pubmed:abstractText
Mice hetero- or homozygously deficient for myelin protein zero (P0+/-, P0-/- mice) are models for distinct forms of inherited de- or dysmyelinating neuropathies, respectively. P0+/- mice show a demyelinating neuropathy with a pathogenetic implication of CD8+ T-lymphocytes and macrophages, while P0-/- mice show dysmyelination with axonal loss. It was, therefore, of interest to treat both mutants with FK506 (Tacrolimus), an agent with immunosuppressive and neuroprotective properties. Treatment of P0+/- mice led to an aggravation of demyelination, without affecting nervous CD8+ T-lymphocytes, but reducing splenic CD4+ cells. Treatment of P0-/- mice resulted in a substantial increase of the dysmyelination-related axon loss. Treatment of wildtype mice did not cause pathological changes in peripheral nerves. Our study shows that FK506 may not be suitable for the treatment of the human nerve disorders. Furthermore, when used as an immunosuppressant, the drug may generate detrimental neurological side effects in patients with an additional hereditary neuropathy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1095-953X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
207-12
pubmed:meshHeading
pubmed-meshheading:19028581-Animals, pubmed-meshheading:19028581-Axons, pubmed-meshheading:19028581-CD4-Positive T-Lymphocytes, pubmed-meshheading:19028581-CD8-Positive T-Lymphocytes, pubmed-meshheading:19028581-Charcot-Marie-Tooth Disease, pubmed-meshheading:19028581-Demyelinating Diseases, pubmed-meshheading:19028581-Disease Models, Animal, pubmed-meshheading:19028581-Flow Cytometry, pubmed-meshheading:19028581-Immunohistochemistry, pubmed-meshheading:19028581-Immunosuppressive Agents, pubmed-meshheading:19028581-Macrophages, pubmed-meshheading:19028581-Mice, pubmed-meshheading:19028581-Mice, Inbred C57BL, pubmed-meshheading:19028581-Mice, Transgenic, pubmed-meshheading:19028581-Microscopy, Electron, pubmed-meshheading:19028581-Myelin P0 Protein, pubmed-meshheading:19028581-Myelin Sheath, pubmed-meshheading:19028581-Neural Conduction, pubmed-meshheading:19028581-Peripheral Nerves, pubmed-meshheading:19028581-Spleen, pubmed-meshheading:19028581-Tacrolimus
pubmed:year
2009
pubmed:articleTitle
Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies.
pubmed:affiliation
Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't