A murine dopamine neuron-specific cDNA library and microarray: increased COX1 expression during methamphetamine neurotoxicity.
Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity.
Barrett
T
T
Research Resources Branch, Laboratory of Genetics, Intramural Research Program, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, Maryland 21224-6825, USA.
Xie
T
T
Piao
Y
Y
Dillon-Carter
O
O
Kargul
G J
GJ
Lim
M K
MK
Chrest
F J
FJ
Wersto
R
R
Rowley
D L
DL
Juhaszova
M
M
Zhou
L
L
Vawter
M P
MP
Becker
K G
KG
Cheadle
C
C
Wood
W H
WH
McCann
U D
UD
Freed
W J
WJ
Ko
M S
MS
Ricaurte
G A
GA
Donovan
D M
DM
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D004298:Dopamine / Q000032:analysis*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D020869:Gene Expression Profiling; D015723:Gene Library; D005813:Genes, Synthetic; D007763:Lac Operon; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D051381:Rats; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D018076:DNA, Complementary; D018765:Dopamine Uptake Inhibitors; D009419:Nerve Tissue Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D003576:Electron Transport Complex IV; D004298:Dopamine