Dopamine Depletion Induces Distinct Compensatory Gene Expression Changes in DARPP-32 Signal Transduction Cascades of Striatonigral and Striatopallidal Neurons
被引:26
作者:
Meurers, Bernhard H.
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h-index: 0
机构:
Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USAUniv Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Meurers, Bernhard H.
[1
,2
]
Dziewczapolski, Gustavo
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h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USAUniv Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Dziewczapolski, Gustavo
[3
,4
]
Shi, Tao
论文数: 0引用数: 0
h-index: 0
机构:
Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USAUniv Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Shi, Tao
[2
]
Bittner, Anton
论文数: 0引用数: 0
h-index: 0
机构:
Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USAUniv Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Bittner, Anton
[2
]
Kamme, Fredrik
论文数: 0引用数: 0
h-index: 0
机构:
Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USAUniv Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Kamme, Fredrik
[2
]
Shults, Clifford W.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USAUniv Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Shults, Clifford W.
[3
,4
]
机构:
[1] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
[2] Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USA
[3] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[4] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA
STRIATAL SYNAPTIC PLASTICITY;
NUCLEUS-ACCUMBENS NEURONS;
MEDIUM SPINY NEURONS;
PARKINSONS-DISEASE;
BASAL GANGLIA;
MOLECULAR CHARACTERIZATION;
MICROARRAY ANALYSIS;
INDUCED DYSKINESIA;
RAT NEOSTRIATUM;
RECEPTOR;
D O I:
10.1523/JNEUROSCI.5310-08.2009
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
Functional alterations in striatal projection neurons play a critical role in the development of motor symptoms in Parkinson's disease (PD), but their molecular adaptation to dopamine depletion remains poorly understood. In particular, type and extent of regulation in postsynaptic signal transduction pathways that determine the responsiveness of striatal projection neurons to incoming stimuli, are currently unknown. Using cell-type-specific transcriptome analyses in a rodent model of chronic dopamine depletion, we identified large-scale gene expression changes, including neurotransmitter receptors, signal transduction cascades, and target proteins of dopamine signaling in striatonigral and striatopallidal neurons. Within the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) cascade of enzymes that plays a central role in signal integration of dopaminoceptive neurons multiple catalytic and regulatory subunits change their mRNA expression levels. In addition to the number of genes the fact that the alterations occur at multiple levels stresses the biological relevance of transcriptional regulation for adaptations of postsynaptic signaling pathways. The overall pattern of changes in both striatonigral and striatopallidal neurons is compatible with homeostatic mechanisms. In accordance with the distinct biological effects of dopamine D-1 and D-2 receptor stimulation, the alterations of the transcriptional profiles most likely result in prodopaminergic phosphorylation patterns. Our data provide insight into the disease-related plasticity of functional genomic networks in vivo that might contribute to the protracted preclinical phase of PD. In addition, the data have potential implications for the symptomatic treatment of the disease.
机构:
Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USARockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Bateup, Helen S.
Svenningsson, Per
论文数: 0引用数: 0
h-index: 0
机构:
Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Karolinska Inst, Dept Physiol & Pharmacol, Ctr Mol Med, S-17177 Stockholm, SwedenRockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Svenningsson, Per
Kuroiwa, Mahomi
论文数: 0引用数: 0
h-index: 0
机构:
Kurume Univ, Sch Med, Dept Pharmacol, Fukuoka 8300011, JapanRockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Kuroiwa, Mahomi
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h-index:
机构:
Gong, Shiaoching
Nishi, Akinori
论文数: 0引用数: 0
h-index: 0
机构:
Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Kurume Univ, Sch Med, Dept Pharmacol, Fukuoka 8300011, JapanRockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Nishi, Akinori
Heintz, Nathaniel
论文数: 0引用数: 0
h-index: 0
机构:
Rockefeller Univ, Mol Biol Lab, New York, NY 10065 USA
Rockefeller Univ, GENSAT Project, New York, NY 10065 USARockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
机构:Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
Beaulieu, JM
Sotnikova, TD
论文数: 0引用数: 0
h-index: 0
机构:Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
Sotnikova, TD
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机构:
Marion, S
Lefkowitz, RJ
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h-index: 0
机构:Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
Lefkowitz, RJ
Gainetdinov, RR
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h-index: 0
机构:Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
Gainetdinov, RR
Caron, MG
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h-index: 0
机构:
Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USADuke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Bertran-Gonzalez, Jesus
Bosch, Clementine
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Bosch, Clementine
Maroteaux, Matthieu
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Maroteaux, Matthieu
Matamales, Miriam
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Matamales, Miriam
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机构:
Herve, Denis
Valjent, Emmanuel
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
机构:
Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USARockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Bateup, Helen S.
Svenningsson, Per
论文数: 0引用数: 0
h-index: 0
机构:
Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Karolinska Inst, Dept Physiol & Pharmacol, Ctr Mol Med, S-17177 Stockholm, SwedenRockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Svenningsson, Per
Kuroiwa, Mahomi
论文数: 0引用数: 0
h-index: 0
机构:
Kurume Univ, Sch Med, Dept Pharmacol, Fukuoka 8300011, JapanRockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Kuroiwa, Mahomi
论文数: 引用数:
h-index:
机构:
Gong, Shiaoching
Nishi, Akinori
论文数: 0引用数: 0
h-index: 0
机构:
Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Kurume Univ, Sch Med, Dept Pharmacol, Fukuoka 8300011, JapanRockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
Nishi, Akinori
Heintz, Nathaniel
论文数: 0引用数: 0
h-index: 0
机构:
Rockefeller Univ, Mol Biol Lab, New York, NY 10065 USA
Rockefeller Univ, GENSAT Project, New York, NY 10065 USARockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA
机构:Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
Beaulieu, JM
Sotnikova, TD
论文数: 0引用数: 0
h-index: 0
机构:Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
Sotnikova, TD
论文数: 引用数:
h-index:
机构:
Marion, S
Lefkowitz, RJ
论文数: 0引用数: 0
h-index: 0
机构:Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
Lefkowitz, RJ
Gainetdinov, RR
论文数: 0引用数: 0
h-index: 0
机构:Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
Gainetdinov, RR
Caron, MG
论文数: 0引用数: 0
h-index: 0
机构:
Duke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USADuke Univ, Med Ctr, Inst Genome Sci & Policy, Ctr Model Human Dis,Dept Cell Biol, Durham, NC 27710 USA
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Bertran-Gonzalez, Jesus
Bosch, Clementine
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Bosch, Clementine
Maroteaux, Matthieu
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Maroteaux, Matthieu
Matamales, Miriam
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Matamales, Miriam
论文数: 引用数:
h-index:
机构:
Herve, Denis
Valjent, Emmanuel
论文数: 0引用数: 0
h-index: 0
机构:
INSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France
Univ Paris 06, F-75005 Paris, FranceINSERM, Inst Fera Moulin, UMR S 839, F-75005 Paris, France