Gene expression profiling of rat midbrain dopamine neurons: implications for selective vulnerability in parkinsonism.
To elucidate factors related to selective dopamine neuron degeneration in Parkinson's disease (PD), we have defined gene expression profiles of discrete dopamine neuron subpopulations in the rat using immunofluorescent laser capture microscopy and microarray analysis. Although profiles were remarkably similar, there are concerted categorical differences in gene expression between dopamine neurons that might explain their differential susceptibility. As a group, energy metabolism transcripts are more highly expressed in substantia nigra (SN) dopamine neurons, an intriguing result considering previous evidence for a mitochondrial defect in idiopathic PD and the greater susceptibility of SN dopamine neurons to damage by mitochondrial poisons. Examination of putative transcription factor binding sites suggests that these concerted differences may be related to differential activity of specific transcription factors. These results provide the first large scale description of gene expression profiles of dopamine neurons and suggest several avenues for investigation into dopaminergic neuroprotective therapy for PD.
Greene
James G
JG
Department of Pharmacology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. jggreen@emory.edu
Dingledine
Raymond
R
Greenamyre
J Timothy
JT
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004298:Dopamine / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D008928:Mitochondria / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020734:Parkinsonian Disorders / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology
D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D004298:Dopamine