Objective <p>Dual-specificity phosphatase 1 (DUSP1) is a negative regulator of mitogen-activated protein kinase (MAPK) activity, and a player in the control of glial function. Several disease models have identified that the expression of DUSP1 is altered in tissue samples, which may contribute to disease pathogenesis. Using post-mortem brain tissue from a cohort of progressive multiple sclerosis (MS) cases, this study set out to determine if the expression of DUSP1 is altered in the brain in MS.</p> Methods <p>We employed the use of a combination of PCR, western immunoblotting and immunohistochemical analysis to profile the expression of DUSP1.</p> Results <p>Data presented herein indicate that DUSP1 is significantly downregulated at gene and protein level in MS white matter tissue, when compared to samples from a non-MS control cohort. We also identify that DUSP1 is expressed on Iba1<sup>+</sup> cells in the brain and that <i>ITGAM</i> (CD11b) expression is elevated in white matter in progressive MS.</p> Conclusions <p>These findings provide evidence that DUSP1 is dysregulated centrally in CNS white matter in progressive MS.</p>

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Downregulation of dual-specificity phosphatase 1 (DUSP1) in post-mortem brain white matter in progressive multiple sclerosis

  • Martí Oró-Nolla,
  • Melody Cui Sun,
  • Thomas Reilly,
  • Julia Anandarajah,
  • Almudena Otálora-Alcaraz,
  • Lisa Costelloe,
  • Hugh Kearney,
  • Richard Magee,
  • Yvonne M. Nolan,
  • Eric J. Downer

摘要

Objective

Dual-specificity phosphatase 1 (DUSP1) is a negative regulator of mitogen-activated protein kinase (MAPK) activity, and a player in the control of glial function. Several disease models have identified that the expression of DUSP1 is altered in tissue samples, which may contribute to disease pathogenesis. Using post-mortem brain tissue from a cohort of progressive multiple sclerosis (MS) cases, this study set out to determine if the expression of DUSP1 is altered in the brain in MS.

Methods

We employed the use of a combination of PCR, western immunoblotting and immunohistochemical analysis to profile the expression of DUSP1.

Results

Data presented herein indicate that DUSP1 is significantly downregulated at gene and protein level in MS white matter tissue, when compared to samples from a non-MS control cohort. We also identify that DUSP1 is expressed on Iba1+ cells in the brain and that ITGAM (CD11b) expression is elevated in white matter in progressive MS.

Conclusions

These findings provide evidence that DUSP1 is dysregulated centrally in CNS white matter in progressive MS.