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Serial analysis of gene expression in the rat striatum following methamphetamine administration.
- Source :
-
Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2006 Aug; Vol. 1074, pp. 13-30. - Publication Year :
- 2006
-
Abstract
- Methamphetamine (METH), a highly addictive drug, can cause degeneration of monoaminergic terminals and neuronal apoptosis in the mammalian brain. In the present article, we have used serial analysis of gene expression (SAGE) to investigate patterns of gene expression in the striata of rats that were given a neurotoxic dose of the drug. SAGE libraries were generated from animals treated with either saline or METH (40 mg/kg) and sacrificed 2 h later. A total of 315 transcripts were differentially expressed between the two libraries (P < 0.05), with 179 (56%) being upregulated and 136 (44%) being downregulated by the METH injection. Of these, CAATT enhancer-binding protein homologous protein (CHOP)/GADD153 (growth arrest- and DNA damage-inducible gene 153) was found to be upregulated by about threefold. Analysis of the expression of genes downstream of CHOP (DOCs) revealed significant METH-induced increases in their expression. Because DOC1 is an analog of carbonic anhydrase (CA) which is involved in the interconversion between carbon dioxide and the bicarbonate ion, we also measured the effects of METH on the expression of several CAs. These were significantly upregulated by METH in a time-dependent fashion. These results indicate that METH toxicity is mediated, in part, by drug-induced perturbations of physiological processes that are dependent on normal pH and CO(2) homeostasis.
- Subjects :
- Animals
Base Sequence
Calcium-Binding Proteins metabolism
Corpus Striatum drug effects
Down-Regulation
Gene Expression Profiling
Molecular Sequence Data
Nerve Tissue Proteins metabolism
Oligonucleotide Array Sequence Analysis
Rats
Rats, Sprague-Dawley
Transcription Factor CHOP metabolism
Up-Regulation
Corpus Striatum metabolism
Dopamine Agents pharmacology
Methamphetamine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0077-8923
- Volume :
- 1074
- Database :
- MEDLINE
- Journal :
- Annals of the New York Academy of Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 17105900
- Full Text :
- https://doi.org/10.1196/annals.1369.002