Alteration of selective neurotransmitters in fetal brains of prenatally alcohol-treated C57BL/6 mice: quantitative analysis using liquid chromatography/tandem mass spectrometry.
We previously demonstrated that prenatal alcohol exposure results in brain defects at different embryonic stages. This study is aimed at characterizing the influence of prenatal alcohol exposure on the levels of several neurotransmitters at early embryonic stage 13 (E13). Pregnant C57BL/6 mice were exposed to either a 25% ethanol derived calorie diet (ALC) or pair-fed (PF) liquid diet from E7 to E13. At E13, fetal brains were collected from dams of the ALC and PF groups. Liquid chromatography/tandem mass spectrometry (LC-MS) was then used to evaluate neurotransmitter levels. This approach involved the use of an LC column in conjunction with multiple-reaction monitoring mass spectrometry. Quantitative analyses of catecholamines, idolamine, and amino acid neurotransmitters revealed significant reductions in the levels of dopamine (p=0.004), norepinephrine (p=0.0009), epinephrine (p=0.0002), serotonin (p=0.004), and GABA (p=0.002) in the ALC group compared to the PF group. However, there was no significant change in the levels of glutamate in E13 fetal brains. These findings demonstrate that prenatal alcohol exposure reduces the concentrations of some catecholamines, idolamine, and amino acid neurotransmitters in E13 fetal brains. This study suggests that alterations of selective neurotransmitters may be the cause of abnormalities in brain function and behavior found in fetal alcohol spectrum disorders.
Sari
Youssef
Y
Program in Neuroscience, Indiana University Bloomington, IN 47405, United States. ysari@indiana.edu <ysari@indiana.edu>
Hammad
Loubna A
LA
Saleh
Marwa M
MM
Rebec
George V
GV
Mechref
Yehia
Y
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology*; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000032:analysis*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*
D018377:Neurotransmitter Agents; D000431:Ethanol