Analysis of methamphetamine-induced changes in the expression of integrin family members in the cortex of wild-type and c-fos knockout mice.
Methamphetamine (METH) is an illicit drug that is also neurotoxic. Recent studies suggest that in addition to dopamine terminal degeneration in the striatum, METH causes apoptosis in cortical neurons. Earlier, we showed that c-fos knockout mice are more susceptible to the toxic effects of the drug. In order to identify possible pathways related to these differences, we have used cDNA array that provided us with a comprehensive catalog of METH affected genes. In the present study, we report on the effects of METH on the integrin family members that were shown to be involved in intracellular signaling cascades effecting cell survival. We found that, in comparison to wild type animals, c-fos knockout mice have lower baseline levels of the integrins in the cortex. Moreover, METH caused time-dependent decreases in their transcripts in both strains of mice. Quantitative RT-PCR confirmed the changes obtained in cDNA array. These findings are discussed in view of the possible role of integrins in METH-induced toxic effects on the cortical neurons.
Betts
Elizabeth S.
ES
Molecular Neuropsychiatry Section, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Krasnova
Irina N.
IN
McCoy
Michael T.
MT
Ladenheim
Bruce
B
Cadet
Jean Lud
JL