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Experimental Methods for Testing the Effects of Neurotrophic Peptide, ADNF-9, Against Alcohol-induced Apoptosis during Pregnancy in C57BL/6 Mice
Published on: April 24, 2013
Cocaine-induced changes in the expression of apoptosis-related genes in the fetal mouse cerebral wall
Svetlana I Novikova1, Fang He, Jie Bai
1Department of Biomedical Sciences, and Program of Neuroscience, University of Maryland, Baltimore, 5-A-12, HHH, 666 W. Baltimore Street, Baltimore, MD 21201, United States.
Abstract:
It has been demonstrated that exposure to cocaine increases cell death in the fetal CNS. To examine the molecular mechanisms of this effect, we employed mouse oligo microarrays followed by real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) to compare expressions of apoptosis-related genes in the cerebral wall of 18-day-old (E18) fetuses from cocaine-treated (20 mg/kg cocaine, s.c., b.i.d., E8th-E18th) and drug-naive (saline, s.c.) mice. Out of approximately 400 relevant genes in the arrays, 53 showed alterations in expression in cocaine-exposed fetuses. Upregulation was observed in 35 proapoptotic and 8 antiapoptotic genes; 4 proapoptotic and 6 antiapoptotic genes were down-regulated. The affected genes encode a wide range of apoptosis-related proteins, including death receptors (NTF-R1, NTF-R2, DR3, DR5, LTbeta-R, GITR, P57 TR-1) and their adaptor and regulatory proteins (MASGE-D1, TRAF-2, SIVA, MET, FLIP, FAIM, IAP1, ATFA), members of transcription regulatory pathways (JNK, NF-kappaB, P53), members of BCL-2 family of proteins (BID, BAD, BAX, BIK, NIP21, NIP3, NIX, BCL-2), DNA damage sensor (PARP-1), caspases and their substrates and regulatory proteins (caspases 8, 4, 9, and 3, ACINUS, CIDE-A, CIDE-B, GAS2), mitochondrially released factors (cytochrome c, AIF, PRG3), specific endoplasmic reticulum- and oxidative stress-associated factors (BACH2, ABL1, ALG2, CHOP), members of cell survival AKT and HSP70 pathways (PIK3GA, PTEN, HSP70, BAG1, BAG2), and others. This suggests that cocaine affects survival of developing cerebral cells via multiple apoptosis-regulating mechanisms.
Insights
Cocaine exposure increases fetal central nervous system (CNS) cell death. This study identified 53 apoptosis-related genes altered in fetal mice exposed to cocaine, revealing multiple molecular mechanisms affecting developing brain cell survival.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Prenatal exposure to cocaine is known to increase fetal central nervous system (CNS) cell death.
- Understanding the molecular mechanisms underlying this effect is crucial for addressing potential developmental consequences.
Purpose of the Study:
- To investigate the molecular mechanisms by which cocaine exposure induces apoptosis in the developing fetal CNS.
- To compare the expression of apoptosis-related genes in the cerebral wall of fetuses exposed to cocaine versus drug-naive controls.
Main Methods:
- Utilized mouse oligo microarrays to screen approximately 400 apoptosis-related genes.
- Employed real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) for validation and precise quantification of gene expression.
- Analyzed gene expression in the cerebral wall of 18-day-old fetuses from cocaine-treated and saline-treated (control) mice.
Main Results:
- Out of 400 genes analyzed, 53 showed significant alterations in expression in cocaine-exposed fetuses.
- Upregulation of 35 proapoptotic and 8 antiapoptotic genes was observed.
- Downregulation of 4 proapoptotic and 6 antiapoptotic genes was noted, affecting diverse pathways including death receptors, BCL-2 family, caspases, and survival pathways.
Conclusions:
- Cocaine exposure significantly impacts the expression of a wide array of apoptosis-related genes in the developing fetal brain.
- These molecular changes suggest that cocaine affects the survival of developing cerebral cells through multiple, complex apoptosis-regulating mechanisms.
