Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies
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−/...
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| Language: | English |
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Elsevier
2009-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996108002532 |
| _version_ | 1818673393417846784 |
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| author | Chi Wang Ip Antje Kroner Bianca Kohl Carsten Wessig Rudolf Martini |
| author_facet | Chi Wang Ip Antje Kroner Bianca Kohl Carsten Wessig Rudolf Martini |
| author_sort | Chi Wang Ip |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-ec8f12ed0e8146b5b481efaaba7b9e4a |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T07:55:05Z |
| publishDate | 2009-02-01 |
| publisher | Elsevier |
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| series | Neurobiology of Disease |
| spelling | doaj.art-ec8f12ed0e8146b5b481efaaba7b9e4a2022-12-21T21:57:45ZengElsevierNeurobiology of Disease1095-953X2009-02-01332207212Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathiesChi Wang Ip0Antje Kroner1Bianca Kohl2Carsten Wessig3Rudolf Martini4Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, GermanyDepartment of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, GermanyDepartment of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, GermanyDepartment of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, GermanyCorresponding author. Fax: +49 931 20123645.; Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, GermanyMice 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.http://www.sciencedirect.com/science/article/pii/S0969996108002532Charcot–Marie–Tooth-diseaseSchwann cellMyelinTreatmentImmunosuppressionNeuroprotection |
| spellingShingle | Chi Wang Ip Antje Kroner Bianca Kohl Carsten Wessig Rudolf Martini Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies Neurobiology of Disease Charcot–Marie–Tooth-disease Schwann cell Myelin Treatment Immunosuppression Neuroprotection |
| title | Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies |
| title_full | Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies |
| title_fullStr | Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies |
| title_full_unstemmed | Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies |
| title_short | Tacrolimus (FK506) causes disease aggravation in models for inherited peripheral myelinopathies |
| title_sort | tacrolimus fk506 causes disease aggravation in models for inherited peripheral myelinopathies |
| topic | Charcot–Marie–Tooth-disease Schwann cell Myelin Treatment Immunosuppression Neuroprotection |
| url | http://www.sciencedirect.com/science/article/pii/S0969996108002532 |
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