PUBLICATION

Developmental stage-dependent deficits induced by embryonic ethanol exposure in zebrafish: A neurochemical analysis

Authors
Facciol, A., Bailleul, C., Nguyen, S., Gerlai, R.
ID
ZDB-PUB-200110-13
Date
2020
Source
Progress in neuro-psychopharmacology & biological psychiatry   99: 109859 (Journal)
Registered Authors
Gerlai, Robert T.
Keywords
Dopamine, FASD, Fetal alcohol spectrum disorders, HPLC, Serotonin, Zebrafish
MeSH Terms
  • 3,4-Dihydroxyphenylacetic Acid/metabolism
  • Animals
  • Brain/drug effects*
  • Brain/embryology
  • Brain/metabolism*
  • Dopamine/metabolism
  • Ethanol/toxicity*
  • Female
  • Fetal Alcohol Spectrum Disorders/metabolism*
  • Hydroxyindoleacetic Acid/metabolism
  • Male
  • Pregnancy
  • Zebrafish
PubMed
31917146 Full text @ Prog. Neuropsychopharmacol. Biol. Psychiatry
Abstract
FASD results from the developing fetus being exposed to alcohol, and is characterized by morphological, behavioural and cognitive deficits. However, the expression, severity and age of onset of these symptoms has been found to show variation. This variation may partly be due to the developmental stage at which alcohol reached the developing fetus. Previously, alcohol was shown to lead to significant concentration dependent behavioural as well as neurochemical changes detected in adult zebrafish when this substance was administered at 24 h post-fertilization (hpf) for 2 h. This alcohol exposure method arguably mimicked the milder, and more prevalent, forms of human FASD. However, whether the observed changes depended upon the developmental stage, i.e., the timing, of alcohol exposure has not been systematically analyzed. Here, we employ the same alcohol dosing regimen, where zebrafish eggs are immersed into 0% or 1% (vol/vol) alcohol for 2 h, but we perform the immersion at 5, 10, 16, 24, 36, or 48 hpf. We previously developed a sensitive HPLC method to quantify neurochemicals, and found levels of dopamine, serotonin and their metabolites DOPAC and 5-HIAA to be affected by embryonic alcohol treatment. Here, using the same method, we compare whole-brain levels of these neurochemicals in the embryonic alcohol exposed and control zebrafish at their age of 30 days post-fertilization (dpf). Consistent with previous reports, we found significant reduction of levels of dopamine, serotonin and their metabolites in the fish exposed to alcohol at 24 hpf. However, we also found significant dependency on the developmental stage at which alcohol was administered with particularly robust impairments when the exposure was at the early or middle of the developmental periods probed. Our results now demonstrate that one can detect functional abnormalities in the zebrafish brain induced by embryonic alcohol as early as 30 dpf and that the neurochemical deficits are dependent upon the developmental stage at which alcohol is administered.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping