A murine dopamine neuron-specific cDNA library and microarray: Increased COXI expression during methamphetamine neurotoxicity

Due to brain tissue heterogeneity, the molecular genetic profile of any neu rotransmitter-specific neuronal subtype is unknown. The purpose of this stu dy was to purify a population of dopamine neurons, construct a cDNA library , and generate an initial gene expression profile and a microarray represen tative of dopamine neuron transcripts. Ventral mesencephalic dopamine neuro ns were purified by fluorescent-activated cell sorting from embryonic day 1 3.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-la cZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced an d arrayed for use in studies of gene expression changes during methamphetam ine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polype ptide I transcript from adult mouse substantial nigra at 12 h posttreatment . This is the first work to describe a gene expression profile for a neuron al subtype and to identify gene expression changes during methamphetamine n eurotoxicity. (C) 2001 Academic Press.