cDNA array analysis of gene expression profiles in the striata of wild-type and Cu/Zn superoxide dismutase transgenic mice treated with neurotoxic doses of amphetamine.
Amphetamine (AMPH) is a drug of abuse that causes the degeneration of striatal dopamine terminals in mammals. Superoxide radicals seem to participate in AMPH-induced damage because its toxicity is attenuated in Cu/Zn superoxide dismutase transgenic (SOD-tg) mice. To provide a detailed analysis of molecular changes associated with AMPH toxicity, we used cDNA arrays consisting of 1176 genes to detect differential changes in gene expression in the striata of wild-type and SOD-tg mice treated with neurotoxic doses of the drug. We found 42 genes that showed >1.8-fold changes in at least two consecutive time points during the course of the study and were differentially affected by AMPH in the two genotypes. Specifically, more transcription factors and genes involved in responses to injury/inflammation were affected in wild-type mice after AMPH administration. Some of these stimulant-induced superoxide-dependent alterations in gene expression might affect neuronal functions and promote neuronal damage. Other changes might help to provide some degree of protection against AMPH toxicity. These results support the view that the use of global array analysis of gene expression will help to identify novel molecular mediators of AMPH-induced neurodegeneration.
Molecular Neuropsychiatry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
Irina N
IN
Krasnova
Michael T
MT
McCoy
Bruce
B
Ladenheim
Jean Lud
JL
Cadet
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*
D011619:Psychotropic Drugs; D012333:RNA, Messenger; D000661:Amphetamine; D013482:Superoxide Dismutase