Neurocognitive Impairment in mdx Mice

Mol Neurobiol. 2019 Nov;56(11):7608-7616. doi: 10.1007/s12035-019-1573-7. Epub 2019 May 10.

Abstract

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that affects muscles and also the brain, resulting in memory and behavioral problems. In the pathogenesis of DMD, inflammation is an important factor during the degenerative process. However, the involvement of the brain is still unclear. Therefore, the objective of this study is to evaluate the cognitive involvement, BDNF levels, cytokine levels through the levels of TNF-α and IL-1β, the myeloperoxidase (MPO) activity, and the expression of proteins postsynaptic density (PSD)-95 and synaptophysin in the brain of mdx mice. To this aim, we used adult mdx mice. It was observed that mdx mice presented deficits on the habituation, aversive, and object recognition memory. These animals also had a depression-like behavior and an anxiety-like behavior, a decrease of BDNF levels, an increase in the levels of TNF-α and IL-1β, an increase of MPO activity, and an overexpression of synaptophysin and PSD-95 in brain tissue. In conclusion, these data show that mdx mice possibly present a neuroinflammatory component and the involvement of synaptic proteins associated to memory storage and restoring process impairment as well as a depressive- and anxiety-like behavior.

Keywords: Cognition; Duchenne muscular dystrophy; Inflammation; Memory and learning; mdx mice.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognition Disorders / pathology*
  • Cytokines / metabolism
  • Habituation, Psychophysiologic
  • Inflammation Mediators / metabolism
  • Male
  • Maze Learning
  • Mice, Inbred mdx
  • Nerve Tissue Proteins / metabolism
  • Peroxidase / metabolism
  • Swimming

Substances

  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Inflammation Mediators
  • Nerve Tissue Proteins
  • Peroxidase