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

PINNA, ANNALISA;Napolitano, F;Pelosi, B;Di Maio, A;Wardas, J;Casu, Ma;COSTA, GIULIA;Migliarini, S;Calabresi, P;Pasqualetti, M;MORELLI, MICAELA;Usiello, A.

2016-01-01

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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.