Transcription factors specifying dopamine phenotype are decreased in cocaine users.
During development, survival of midbrain dopamine neurons and specification of their phenotype are dependent upon the intracellular expression of a number of transcription factors, including Engrailed 1, Pitx3, and Nurr1. The role of these transcription factors in the maintenance of the dopaminergic phenotype is less clear. In the present study, we show that each of these transcription factors is robustly expressed in adult dopamine neurons in human midbrain, and that cocaine abuse is associated with a significant decrease in the abundance of Nurr1 and Pitx3 in these cells. These data suggest that cocaine abuse leads to a partial loss of dopaminergic phenotype.
Bannon
Michael J
MJ
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 540 E. Canfield, Rm. 2309 Scott Hall, Detroit, MI 48201, USA. mbannon@med.wayne.edu
Pruetz
Barb
B
Barfield
Elaine
E
Schmidt
Carl J
CJ
D019970:Cocaine-Related Disorders / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004298:Dopamine / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000502:physiology; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010641:Phenotype; D016707:Tissue Fixation; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors; C433629:homeobox protein PITX3; D004298:Dopamine