Distinct gene expression signatures in the striata of wild-type and heterozygous c-fos knockout mice following methamphetamine administration: evidence from cDNA array analyses.
Methamphetamine (METH) is a drug of abuse which can cause apoptosis and degeneration of monoaminergic terminals in the mammalian brain. c-fos appears to play a protective role against METH-induced damage because METH toxicity is exacerbated in c-fos heterozygous knockout mice. In the present study, we used the comprehensive technique of cDNA array to test the idea that heterozygous c-fos knockout mice might show differential METH-induced molecular responses in comparison to wild-type (WT) animals. Of 1,176 genes examined, the expression of 195 genes in either of the two groups of mice was affected by at least 2-fold at 2 or 12 h after METH treatment. More genes were either up- or downregulated in the WT mice. Moreover, there were substantial differences in the pattern of responses between the two genotypes, with more genes involved in DNA repair and protective processes being upregulated in WT mice after METH administration. These results support the idea that the c-fos knockout genotype may render the animals unable to trigger multicomponent responses in order to protect against the multifaceted toxic effects of this illicit neurotoxin.
Cadet
Jean Lud
JL
Molecular Neuropsychiatry Section, Intramural Research Program, NIH/NIDA, PO Box 5180, Baltimore, MD 21224, USA. jcadet@intra.nida.nih.gov
McCoy
Michael T
MT
Ladenheim
Bruce
B
D000818:Animals; D016000:Cluster Analysis; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D015342:DNA Probes; D004260:DNA Repair / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics*; D017403:In Situ Hybridization; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D015854:Up-Regulation / Q000187:drug effects
D015342:DNA Probes; D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; D004247:DNA