The Small GTP-Binding Protein Rhes Influences Nigrostriatal-Dependent Motor Behavior During Aging

Mov Disord. 2016 Apr;31(4):583-9. doi: 10.1002/mds.26489. Epub 2016 Feb 8.

Abstract

Background: Here we aimed to evaluate: (1) Rhes mRNA expression in mouse midbrain, (2) the effect of Rhes deletion on the number of dopamine neurons, (3) nigrostriatal-sensitive behavior during aging in knockout mice.

Methods: Radioactive in situ hybridization was assessed in adult mice. The beam-walking test was executed in 3-, 6- and 12-month-old mice. Immunohistochemistry of midbrain tyrosine hydroxylase (TH)-positive neurons was performed in 6- and 12-month-old mice.

Results: Rhes mRNA is expressed in TH-positive neurons of SNpc and the ventral tegmental area. Moreover, lack of Rhes leads to roughly a 20% loss of nigral TH-positive neurons in both 6- and 12-month-old mutants, when compared with their age-matched controls. Finally, lack of Rhes triggers subtle alterations in motor performance and coordination during aging.

Conclusions: Our findings indicate a fine-tuning role of Rhes in regulating the number of TH-positive neurons of the substantia nigra and nigrostriatal-sensitive motor behavior during aging.

Keywords: Rasd2; Rhes; TH-positive neurons; dopamine neurons; midbrain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Behavior, Animal / physiology
  • Corpus Striatum / metabolism*
  • Dopaminergic Neurons / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Psychomotor Performance / physiology*
  • Substantia Nigra / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Tyrosine 3-Monooxygenase
  • GTP-Binding Proteins
  • Rasd2 protein, mouse