| First Author | Sasaki K | Year | 2013 |
| Journal | J Neurochem | Volume | 124 |
| Issue | 6 | Pages | 844-54 |
| PubMed ID | 23311775 | Mgi Jnum | J:193905 |
| Mgi Id | MGI:5469908 | Doi | 10.1111/jnc.12149 |
| Citation | Sasaki K, et al. (2013) Age-dependent dystonia in striatal Ggamma7 deficient mice is reversed by the dopamine D2 receptor agonist pramipexole. J Neurochem 124(6):844-54 |
| abstractText | Ggamma7 is enriched in striatum and forms a heterotrimeric complex with Galpha /Gbeta, which is coupled to D1 receptor (D1R). Here, we attempted to characterize the pathophysiological, neurochemical, and pharmacological features of mice deficient of Ggamma7 gene. Ggamma7 knockout mice exhibited age-dependent deficiency in rotarod behavior and increased dystonia-like clasping reflex without loss of striatal neurons. The neurochemical basis for the motor manifestations using immunoblot analysis revealed increased levels of D1R, ChAT and NMDA receptor subunits (NR1 and NR2B) concurrent with decreased levels of D2R and Galpha , possibly because of the secondary changes of decreased Galpha /Ggamma7-mediated D1R transmission. These behavioral and neurochemical changes are closely related to those observed in Huntington's disease (HD) human subjects and HD model mice. Taking advantage of the finding of D2R down-regulation in Ggamma7 knockout mice and the dopamine-mediated synergistic relationship in the control of locomotion between D2R-striatopallidal and D1R-stritonigral neurons, we hypothesized that D2-agonist pramipexole would reverse behavioral dyskinesia caused by defective D1R/Galpha signaling. Indeed, the rotarod deficiency and clasping reflex were reversed by pramipexole treatment under chronic administration. These findings suggest that Ggamma7 knockout mice could be a new type of movement disorders, including HD and useful for the evaluation of therapeutic candidates. |
