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Decrease in prosaposin in the Dystrophic mdx mouse brain.

Hui-Ling Gao1, Cheng Li, Hiroaki Nabeka

  • 1Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan ; College of Life and Health Sciences, Northeastern University, Shenyang, China.

Plos One
|November 19, 2013
PubMed
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Duchenne muscular dystrophy in mdx mice is linked to lower prosaposin (PS) levels in the brain, suggesting PS plays a role in the neurological pathology associated with this condition.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Duchenne muscular dystrophy (DMD) results from dystrophin gene mutations, causing brain metabolic and structural issues.
  • Dystrophin deficiency in the brain is linked to impaired cognitive function.
  • Prosaposin (PS), a neurotrophic factor, is found in brain regions and the choroid plexus.

Purpose of the Study:

  • To investigate the role of prosaposin (PS) in the brain abnormalities observed in mdx mice, a model for Duchenne muscular dystrophy.
  • To determine if PS levels correlate with dystrophin loss and brain pathology.

Main Methods:

  • Immunochemistry, Western blotting, and in situ hybridization were used to analyze PS distribution and levels in mdx mouse brains.
  • Analysis included cerebral cortex, hippocampus, cerebellum, and choroid plexus.

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  • Mitogen-activated protein kinase (MAPK) signaling, specifically ERK1/2, was also investigated.
  • Main Results:

    • Lower levels of prosaposin (PS) were detected in neurons and the choroid plexus of mdx mice compared to controls.
    • PS mRNA levels (Pro+9) were also reduced in key brain regions of mdx mice.
    • Increased ERK1/2 activation was observed in mdx mice, correlating positively with PS activity.

    Conclusions:

    • Reduced prosaposin (PS) levels are associated with brain pathology in mdx mice.
    • These findings suggest PS is involved in the neurological consequences of Duchenne muscular dystrophy.
    • The study highlights a potential link between dystrophin deficiency, PS, and brain dysfunction.