Changes in cytoskeletal gene expression linked to MPTP-treatment in Mice.
Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and a marked reduction of dopamine (DA) levels in the striatum. Binding to its specific receptors, DA switches on a complex program of intracellular signaling that regulates gene expression. We evaluated the changes in striatal gene expression in a mouse model of Parkinson's disease, using differential display analysis. The mRNA for the cytoskeleton family proteins, radixin, cofilin and centractin/ARP-1, was abnormally expressed in the striatum of these MPTP-treated mice. Moreover, we also found that radixin mRNA and its protein levels are under DA control through specific D1-dopaminergic receptors in a dose- and time-dependent manner in the GT1-7 neural cell line. These findings suggest a role for DA for regulation of cytoskeletal proteins involved in the integrity and function of synapsis.
Cuadrado-Tejedor
Mar
M
Area de Neurociencias, Centro de Investigación Médica Aplicada, Facultad de Medicina, Universidad de Navarra, Avda de Pio XII 55, 31080 Pamplona, Spain.
Sesma
M Teresa
MT
Giménez-Amaya
José Manuel
JM
Ortiz
Lourdes
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; C071776:radixin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000242:Cyclic AMP; D004298:Dopamine