The goal of the proposal is to assess the teratogenic effects of marijuana on the developing nervous system. Marijuana is the most commonly used illicit drug by pregnant women. Its major psychoactive constituent, THC, crosses the placenta and accumulates in fetal brain, potentially harming CNS development, marijuana use in early pregnancy is associated with miscarriage and cognitive abnormalities at age 10 in the offspring, such as lower IQ and learning disabilities, memory impairment and ADHD. Animal models show that THC exposure at a period corresponding to weeks two-three of human pregnancy, results in teratogenesis of the developing nervous system. At this time point, most women are unaware of their pregnancy, and thus of the potentially harmful effects of marijuana. We propose to use a combination of microsurgical, pharmacological and molecular approaches using chick as an animal model, to characterize the embryotoxic effects of marijuana on the initial steps of brain development. This research will provide information for a better understanding of the risks of marijuana exposure during early pregnancy, and will serve as a basis for teratogenic studies involving other drugs of abuse, such as alcohol, cocaine, metamphetamine and opiates, or combinations thereof.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA021977-02
Application #
7682128
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2008-09-01
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
2
Fiscal Year
2009
Total Cost
$59,402
Indirect Cost
Name
Texas A&M University
Department
Type
Schools of Medicine
DUNS #
835607441
City
College Station
State
TX
Country
United States
Zip Code
77845
Nagre, Nagaraja N; Subbanna, Shivakumar; Shivakumar, Madhu et al. (2015) CB1-receptor knockout neonatal mice are protected against ethanol-induced impairments of DNMT1, DNMT3A, and DNA methylation. J Neurochem 132:429-442
Subbanna, Shivakumar; Psychoyos, Delphine; Xie, Shan et al. (2015) Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice. J Neurochem 134:276-87
Subbanna, S; Nagre, N N; Shivakumar, M et al. (2014) Ethanol induced acetylation of histone at G9a exon1 and G9a-mediated histone H3 dimethylation leads to neurodegeneration in neonatal mice. Neuroscience 258:422-32
Subbanna, Shivakumar; Shivakumar, Madhu; Umapathy, Nagavedi S et al. (2013) G9a-mediated histone methylation regulates ethanol-induced neurodegeneration in the neonatal mouse brain. Neurobiol Dis 54:475-85
Subbanna, Shivakumar; Shivakumar, Madhu; Psychoyos, Delphine et al. (2013) Anandamide-CB1 receptor signaling contributes to postnatal ethanol-induced neonatal neurodegeneration, adult synaptic, and memory deficits. J Neurosci 33:6350-66
Psychoyos, Delphine; Vinod, K Yaragudri (2013) Marijuana, Spice 'herbal high', and early neural development: implications for rescheduling and legalization. Drug Test Anal 5:27-45
Vinod, K Yaragudri; Xie, Shan; Psychoyos, Delphine et al. (2012) Dysfunction in fatty acid amide hydrolase is associated with depressive-like behavior in Wistar Kyoto rats. PLoS One 7:e36743
Psychoyos, Delphine; Vinod, K Yaragudri; Cao, Jin et al. (2012) Cannabinoid receptor 1 signaling in embryo neurodevelopment. Birth Defects Res B Dev Reprod Toxicol 95:137-50
Psychoyos, Delphine; Finnell, Richard (2009) Assay for neural induction in the chick embryo. J Vis Exp :
Psychoyos, Delphine; Finnell, Richard (2009) Method for whole mount antibody staining in chick. J Vis Exp :

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