Hippocampal transcriptome reveals novel targets of FASD pathogenesis.
Animals
Disease Models, Animal
Ethanol
/ administration & dosage
Female
Fetal Alcohol Spectrum Disorders
/ pathology
High-Throughput Nucleotide Sequencing
/ methods
Hippocampus
/ pathology
Male
Pregnancy
Prenatal Exposure Delayed Effects
/ chemically induced
Rats
Rats, Sprague-Dawley
Transcriptome
/ drug effects
brain
hippocampus
nitric oxide
pregnancy
teratology
Journal
Brain and behavior
ISSN: 2162-3279
Titre abrégé: Brain Behav
Pays: United States
ID NLM: 101570837
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
11
04
2019
revised:
01
05
2019
accepted:
06
05
2019
pubmed:
30
5
2019
medline:
20
3
2020
entrez:
30
5
2019
Statut:
ppublish
Résumé
Prenatal alcohol exposure can contribute to fetal alcohol spectrum disorders (FASD), characterized by a myriad of developmental impairments affecting behavior and cognition. Studies show that many of these functional impairments are associated with the hippocampus, a structure exhibiting exquisite vulnerability to developmental alcohol exposure and critically implicated in learning and memory; however, mechanisms underlying alcohol-induced hippocampal deficits remain poorly understood. By utilizing a high-throughput RNA-sequencing (RNA-seq) approach to address the neurobiological and molecular basis of prenatal alcohol-induced hippocampal functional deficits, we hypothesized that chronic binge prenatal alcohol exposure alters gene expression and global molecular pathways in the fetal hippocampus. Timed-pregnant Sprague-Dawley rats were randomly assigned to a pair-fed control (PF) or binge alcohol (ALC) treatment group on gestational day (GD) 4. ALC dams acclimatized from GDs 5-10 with a daily treatment of 4.5 g/kg alcohol and subsequently received 6 g/kg on GDs 11-20. PF dams received a once daily maltose dextrin gavage on GDs 5-20, isocalorically matching ALC counterparts. On GD 21, bilateral hippocampi were dissected, flash frozen, and stored at -80 RNA-seq identified 13,388 genes, of these, 76 genes showed a significant difference (p < 0.05, log2 fold change ≥2) in expression between the PF and ALC groups. Forty-nine genes showed sex-dependent dysregulation; IPA analysis showed among female offspring, dysregulated pathways included proline and citrulline biosynthesis, whereas in males, xenobiotic metabolism signaling and alaninine biosynthesis etc. were altered. We conclude that chronic binge alcohol exposure during pregnancy dysregulates fetal hippocampal gene expression in a sex-specific manner. Identification of subtle, transcriptome-level dysregulation in hippocampal molecular pathways offers potential mechanistic insights underlying FASD pathogenesis.
Identifiants
pubmed: 31140755
doi: 10.1002/brb3.1334
pmc: PMC6625466
doi:
Substances chimiques
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e01334Informations de copyright
© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
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