| First Author | Park HY | Year | 2016 |
| Journal | Neurobiol Dis | Volume | 89 |
| Pages | 169-79 | PubMed ID | 26875664 |
| Mgi Jnum | J:240859 | Mgi Id | MGI:5896514 |
| Doi | 10.1016/j.nbd.2016.02.013 | Citation | Park HY, et al. (2016) Gadd45beta ameliorates L-DOPA-induced dyskinesia in a Parkinson's disease mouse model. Neurobiol Dis 89:169-79 |
| abstractText | The dopamine precursor 3,4-dihydroxyphenyl-l-alanine (L-DOPA) is currently the most efficacious pharmacotherapy for Parkinson's disease (PD). However, long-term L-DOPA treatment leads to the development of abnormal involuntary movements (AIMs) in patients and animal models of PD. Recently, involvement of growth arrest and DNA damage-inducible 45beta (Gadd45beta) was reported in neurological and neurobehavioral dysfunctions. However, little is known about the role of Gadd45beta in the dopaminergic nigrostriatal pathway or L-DOPA-induced dyskinesia (LID). To address this issue, we prepared an animal model of PD using unilateral 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra of Gadd45beta(+/+) and Gadd45beta(-/-) mice. Dyskinetic symptoms were triggered by repetitive administration of L-DOPA in these 6-OHDA-lesioned mice. Whereas dopamine denervation in the dorsal striatum decreased Gadd45beta mRNA, chronic L-DOPA treatment significantly increased Gadd45beta mRNA expression in the 6-OHDA-lesioned striatum of wild-type mice. Using unilaterally 6-OHDA-lesioned Gadd45beta(+/+) and Gadd45beta(-/-) mice, we found that mice lacking Gadd45beta exhibited long-lasting increases in AIMs following repeated administration of L-DOPA. By contrast, adeno-associated virus-mediated expression of Gadd45beta in the striatum reduced AIMs in Gadd45beta knockout mice. The deficiency of Gadd45beta in LID increased expression of DeltaFosB and c-Fos in the lesioned striatum 90 min after the last administration of L-DOPA following 11days of daily L-DOPA treatments. These data suggest that the increased expression of Gadd45beta induced by repeated administration of L-DOPA may be beneficial in patients with PD. |
