| First Author | Alcacer C | Year | 2014 |
| Journal | Neurosci Lett | Volume | 583 |
| Pages | 76-80 | PubMed ID | 25233866 |
| Mgi Jnum | J:215540 | Mgi Id | MGI:5605604 |
| Doi | 10.1016/j.neulet.2014.09.018 | Citation | Alcacer C, et al. (2014) Mitogen- and stress-activated protein kinase 1 is required for specific signaling responses in dopamine-denervated mouse striatum, but is not necessary for l-DOPA-induced dyskinesia. Neurosci Lett 583:76-80 |
| abstractText | In advanced Parkinson's disease, l-DOPA treatment causes the appearance of abnormal involuntary movements or l-DOPA-induced dyskinesia (LID). LID results in part from l-DOPA-induced activation of extracellular signal-regulated kinase (ERK) in the dopamine-denervated striatum. Activated ERK triggers nuclear responses, including phosphorylation of mitogen- and stress-activated protein kinase 1 (MSK1) and histone H3, and transcription of genes such as FosB. To determine the role of MSK1, wild type and MSK1 knockout mice with unilateral 6-hydroxydopamine lesion in the dorsolateral striatum were chronically treated with l-DOPA. The absence of MSK1 had no effect on the lesion or l-DOPA-induced ERK activation, but reduced l-DOPA-induced phosphorylation of histone H3 and FosB accumulation in the dopamine-denervated striatum. MSK1 deficiency also prevented the increase in Galphaolf, the stimulatory alpha subunit of G protein coupling striatal dopamine D1 receptor to adenylyl cyclase. However, the intensity of LID was similar in MSK1-deficient and wild type mice. In conclusion, l-DOPA-induced activation of MSK1 contributes to histone H3 phosphorylation, induction of FosB, and Galphaolf up-regulation but appears not to be necessary for the development of LID. |
