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Cocaine selectively alters neurotransmitter receptor mRNAs in mouse embryos
S A Mackler1, G D Bennett, V P Tsuei
1Division of General Internal Medicine, University of Pennsylvania, Philadelphia, USA.
Abstract:
Alterations in gene expression due to in utero cocaine exposure may adversely affect nervous system development. The present study examined whether or not cocaine administration to pregnant mice alters embryonic mRNA levels for several developmentally-regulated genes. Antisense RNA amplification was performed using RNA from LM/Bc embryos at gestational days 9.5 and 10.5 after three days of cocaine treatment. This technique highlights simultaneous changes that occur in the expression of many genes after a teratogenic insult. Significant changes occurred in the expression pattern on only four genes from a total of 42 candidate cDNAs. These included increases in the relative levels of the alpha and beta 1 subunits of the GABAA receptor without concurrent changes in the non-NMDA glutamate receptor subunits. The results support the hypothesis that in utero cocaine exposure leads to specific changes in gene expression that may ultimately contribute to developmental abnormalities.
Insights
In utero cocaine exposure alters gene expression in developing embryos, specifically affecting GABAA receptor subunits. These changes may contribute to nervous system developmental abnormalities.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- In utero exposure to substances like cocaine can disrupt normal nervous system development.
- Understanding the molecular mechanisms, particularly gene expression changes, is crucial for identifying potential developmental abnormalities.
Purpose of the Study:
- To investigate the impact of maternal cocaine administration on embryonic gene expression.
- To identify specific developmentally-regulated genes affected by prenatal cocaine exposure.
Main Methods:
- Pregnant mice were treated with cocaine.
- Antisense RNA amplification was used to analyze mRNA levels from embryonic samples at specific gestational days (9.5 and 10.5).
- Expression patterns of 42 candidate cDNAs were assessed.
Main Results:
- Significant alterations in gene expression were observed for four out of 42 candidate genes.
- Increased mRNA levels for alpha and beta 1 subunits of the GABAA receptor were noted.
- No concurrent changes were found in the expression of non-NMDA glutamate receptor subunits.
Conclusions:
- Prenatal cocaine exposure induces specific changes in embryonic gene expression.
- Altered expression of GABAA receptor subunits may play a role in cocaine-induced developmental abnormalities of the nervous system.