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Title: Gene-specific of endocannabinoid receptor 1 (cnr1a) by ethanol probably leads to the development of fetal alcohol spectrum disorder (FASD) phenotypes in Japanese rice fish (Oryzias latipes) embryogenesis

Author
item DASMAHAPATRA, ASOK - University Of Mississippi
item KHAN, IKHLAS - University Of Mississippi

Submitted to: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2014
Publication Date: 1/22/2015
Citation: Dasmahapatra, A.K., Khan, I.A. 2015. Gene-specific of endocannabinoid receptor 1 (cnr1a) by ethanol probably leads to the development of fetal alcohol spectrum disorder (FASD) phenotypes in Japanese rice fish (Oryzias latipes) embryogenesis. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 167:90-100.

Interpretive Summary: Alcohol consumption by women during pregnancy often induces fetal alcohol spectrum disorder (FASD) in children. Molecular mechanism or prevention of FASD, other than women abstaining from alcohol drinking during pregnancy, is not known. FASD is a neurobehavioral disorder we therefore are searching a molecular target in the developing brain. Moreover, a limitation of the use of synthetic anti-alcoholic drugs during pregnancy our long term goal is to investigate on botanicals that have therapeutic potential for the treatment of alcoholism and thus FASD. We used Japanese rice fish (Oryzias latipes) as an animal model of FASD and cannabinoid receptor (cnr) genes as molecular target of brain function. Our study indicates that Japanese rice fish embryos expressed three human ortholog CB receptor genes during development and alcohol is able to attenuate the expression of cnr1a gene. Therefore cnr1a genes should be a potential target of FASD and will be used for screening of botanicals for the discovery of antialcoholic drugs.

Technical Abstract: Developmental ethanol exposure is able to induce Fetal Alcohol Spectrum Disorder (FASD) phenotypes in Japanese rice fish (Oryzias latipes). This study investigated possible differential expression of cannabinoid receptor (cnr) mRNAs during Japanese rice fish embryogenesis and variability to ethanol-induced FASD phenotypes. Extensive searching of public data bases (GenBank, Ensembl) indicates that Japanese rice fish genome includes three human ortholog CNR genes (cnr1a, cnr1b and cnr2). A quantitative real-time PCR (qPCR) technique was used to analyze the expression of these three cnr genes during Japanese rice fish embryogenesis and their response to developmental ethanol exposure. qPCR analyses indicate that the expression of all three cnr is developmentally regulated and only cnr2 mRNA showed maternal expression. The mRNA concentrations of all three receptors were found to be enhanced after 3 dpf and attained maximal level either prior to or after hatching. Short period (0-2 dpf) exposure of the embryos to ethanol (300 mM) is unable to produce any significant effect in cnr gene expression immediately after ethanol removal; however, if these embryos were maintained in clean hatching solution without ethanol for another four days (6 dpf), only cnr1a mRNA content was reduced significantly in comparison to controls. Expression of other two cnr mRNAs (cnr1b and cnr2) either in 2 dpf or in 6 dpf remained at the same level as in controls. Continuous exposure (0-6 dpf) of the embryos to ethanol (300 mM) is also showed significant reduction in cnr1a mRNA content; however, cnr1b and cnr2 mRNAs maintained the same status as in the controls. Conclusions: Among the three cnrs, ethanol disrupts the expression of only cnr1a that may probably lead the development of FASD phenotypes in Japanese rice fish.