کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6274790 1614829 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Upregulation of voltage-gated Ca2+ channels in mouse astrocytes infected with Theiler's murine encephalomyelitis virus (TMEV)
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Upregulation of voltage-gated Ca2+ channels in mouse astrocytes infected with Theiler's murine encephalomyelitis virus (TMEV)
چکیده انگلیسی


- Theiler's murine encephalomyelitis virus (TMEV) induces demyelination in susceptible strains of mice.
- TMEV infection syndrome is a model system to study multiple sclerosis.
- An overexpression of genes for Ca2+ channels in TMV infected mouse astrocytes was observed.
- DNA hybridization, Western blotting and RT-PCR and qRT-PCR showed an increased expression of Ca2+ channel subunits.
- Functional L- and N-type Ca2+ currents were shown to be upregulated in TMV infected astrocytes.

Theiler's murine encephalomyelitis virus (TMEV) induces demyelination in susceptible strains of mice through a CD4+ Th1 T cell-mediated immunopathological process. TMEV infection produces a syndrome in mice that resembles multiple sclerosis. In this work, we focused on the increased expression of the genes encoding voltage-gated Ca2+ channel subunits in SJL/J mouse astrocytes infected in culture with a BeAn strain of TMEV. Affymetrix DNA murine genome U74v2 DNA microarray hybridized with cRNA from mock- and TMEV-infected astrocytes revealed the upregulation of four sequences encoding Ca2+-binding and Ca2+ channel subunit proteins. The DNA hybridization results were further validated using conventional RT-PCR and quantitative RT-PCR, demonstrating the increased expression of mRNA encoding channel subunit proteins. Western blotting also showed the increased synthesis of L- and N-type channel subunit specific proteins after infection. The reduced expression and the functional upregulation of functional voltage-gated Ca2+ channels in mock- and TMEV-infected cells, respectively, was demonstrated using voltage clamp experiments. TMEV infection in mouse astrocytes induced a Ca2+ current with a density proportional to the amount of viral particles used for infection. The use of Ca2+ channel blockers, nimodipine and ω-conotoxin-GVIA, showed that both functional L- and N-type Ca2+ channels were upregulated in infected astrocytes. The upregulation of Ca2+ channels in astrocytes after TMEV infection provides insight into the molecular processes and potential role of astrocyte Ca2+ dysregulation in the pathophysiology of encephalomyelitis and is important for the development of novel therapeutic strategies leading to prevention of neurodegeneration.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 247, 5 September 2013, Pages 309-318
نویسندگان
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