Developmental alterations in motor coordination and medium spiny neuron markers in mice lacking pgc-1α.
Developmental alterations in motor coordination and medium spiny neuron markers in mice lacking pgc-1α.
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DOI：
10.1371/journal.pone.0042878
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cowell RM
中科院分区：
文献类型：
--
作者：
Lucas EK;Dougherty SE;McMeekin LJ;Trinh AT;Reid CS;Cowell RM
Accumulating evidence implicates the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) in the pathophysiology of Huntington Disease (HD). Adult PGC-1α −/− mice exhibit striatal neurodegeneration, and reductions in the expression of PGC-1α have been observed in striatum and muscle of HD patients as well as in animal models of the disease. However, it is unknown whether decreased expression of PGC-1α alone is sufficient to lead to the motor phenotype and striatal pathology characteristic of HD. For the first time, we show that young PGC-1α −/− mice exhibit severe rotarod deficits, decreased rearing behavior, and increased occurrence of tremor in addition to the previously described hindlimb clasping. Motor impairment and striatal vacuolation are apparent in PGC-1α −/− mice by four weeks of age and do not improve or decline by twelve weeks of age. The behavioral and pathological phenotype of PGC-1α −/− mice can be completely recapitulated by conditional nervous system deletion of PGC-1α, indicating that peripheral effects are not responsible for the observed abnormalities. Evaluation of the transcriptional profile of PGC-1α −/− striatal neuron populations and comparison to striatal neuron profiles of R6/2 HD mice revealed that PGC-1α deficiency alone is not sufficient to cause the transcriptional changes observed in this HD mouse model. In contrast to R6/2 HD mice, PGC-1α −/− mice show increases in the expression of medium spiny neuron (MSN) markers with age, suggesting that the observed behavioral and structural abnormalities are not primarily due to MSN loss, the defining pathological feature of HD. These results indicate that PGC-1α is required for the proper development of motor circuitry and transcriptional homeostasis in MSNs and that developmental disruption of PGC-1α leads to long-term alterations in motor functioning.
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影响因子：
15.1
作者：
Che HV;Metzger S;Portal E;Deyle C;Riess O;Nguyen HP
通讯作者：
Nguyen HP
通过基础神经节电路的光遗传控制对帕金森运动行为的调节。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.82.24.8780
发表时间：
1985-12-01
影响因子：
11.1
作者：
GERFEN, CR;BAIMBRIDGE, KG;MILLER, JJ
通讯作者：
MILLER, JJ
DOI：
10.1073/pnas.88.10.4205
发表时间：
1991-05-01
影响因子：
11.1
作者：
LEMOINE, C;NORMAND, E;BLOCH, B
通讯作者：
BLOCH, B
影响因子：
1.7
作者：
KUBOTA, Y;MIKAWA, S;KAWAGUCHI, Y
通讯作者：
KAWAGUCHI, Y