Location: Natural Products Utilization ResearchTitle: Developmental regulation of neuroligin genes in Japanese rice fish (oryzias latipes) embryogenesis maintains the rhythym during ethanol-in Author
Submitted to: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/5/2013
Publication Date: 1/1/2014
Citation: Haron, M.H., Khan, I.A., Dasmahapatra, A.K. 2014. Developmental regulation of neuroligin genes in Japanese rice fish (oryzias latipes) embryogenesis maintains the rhythym during ethanol-in. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 159C:62-68. 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 neuroligin gene (nlgn) as a molecular target of brain function. Our study indicates that medaka embryos expressed six human ortholog nlgn genes during development; however, alcohol is unable to attenuate the effect. Therefore nlgn genes are not the potential target of FASD.
Technical Abstract: Although prenatal alcohol exposure is the potential cause of fetal alcohol spectrum disorder (FASD) in humans, the molecular mechanism(s) of FASD is yet unknown. We have used Japanese rice fish (Oryzias latipes) embryogenesis as an animal model of FASD and reported that this model has effectively generated several phenotypic features in the cardiovasculature and neurocranial cartilages by developmental ethanol exposure which is analogous to human FASD phenotypes. As FASD is a neurobehavioral disorder, we are searching a molecular target of ethanol that alters neurological functions. In this communication, we have focused on neuroligin genes (nlgn) which are known to be active at the postsynaptic side of both excitatory and inhibitory synapses of the central nervous system. There are six human NLGN homologs of Japanese rice fish reported in public data bases. We have partially cloned these genes and analyzed their expression pattern during normal development and also after exposing the embryos to ethanol. Our data indicate that the expression of all six nlgn genes in Japanese rice fish embryos is developmentally regulated. Although ethanol is able to induce developmental abnormalities in Japanese rice fish embryogenesis comparable to the FASD phenotypes, quantitative real-time PCR (qPCR) analysis of nlgn mRNAs indicate an unresponsiveness of these genes to ethanol. We conclude that the disruption of the developmental rhythm of Japanese rice fish embryogenesis by ethanol that lead to FASD may not affect the nlgn gene expression at the message level.