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Reproductive toxicology (Elmsford, N.Y.)
03, 2018;76 84-92.

Fetal regional brain protein signature in FASD rat model.

Katie L Davis-Anderson, Hendrik Wesseling, Lara M Siebert, Emilie R Lunde-Young, Vishal D Naik, Hanno Steen, Jayanth Ramadoss
Author Information
  1. Katie L Davis-Anderson: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4466, USA.
  2. Hendrik Wesseling: Departments of Pathology, Harvard Medical School and Boston Children's Hospital, Boston, MA 02115, USA.
  3. Lara M Siebert: Departments of Pathology, Harvard Medical School and Boston Children's Hospital, Boston, MA 02115, USA.
  4. Emilie R Lunde-Young: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4466, USA.
  5. Vishal D Naik: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4466, USA.
  6. Hanno Steen: Departments of Pathology, Harvard Medical School and Boston Children's Hospital, Boston, MA 02115, USA.
  7. Jayanth Ramadoss: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4466, USA. Electronic address: jramadoss@cvm.tamu.edu.
PMID: 29408587 DOI: 10.1016/j.reprotox.2018.01.004

Abstract

Fetal alcohol spectrum disorders (FASD) describe neurodevelopmental deficits in children exposed to alcohol in utero. We hypothesized that gestational alcohol significantly alters fetal brain regional protein signature. Pregnant rats were binge-treated with alcohol or pair-fed and nutritionally-controlled. Mass spectrometry identified 1806, 2077, and 1456 quantifiable proteins in the fetal hippocampus, cortex, and cerebellum, respectively. A stronger effect of alcohol exposure on the hippocampal proteome was noted: over 600 hippocampal proteins were significantly (P < .05) altered, including annexin A2, nucleobindin-1, and glypican-4, regulators of cellular growth and developmental morphogenesis. In the cerebellum, cadherin-13, reticulocalbin-2, and ankyrin-2 (axonal growth regulators) were significantly (P < .05) altered; altered cortical proteins were involved in autophagy (endophilin-B1, synaptotagmin-1). Ingenuity analysis identified proteins involved in protein homeostasis, oxidative stress, mitochondrial dysfunction, and mTOR as major pathways in the cortex and hippocampus significantly (P < .05) affected by alcohol. Thus, neurodevelopmental protein changes may directly relate to FASD neuropathology.

Keywords

Alcohol FASD Fetal Teratology

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Grants

  1. K99 AA019446/NIAAA NIH HHS
  2. R00 AA019446/NIAAA NIH HHS
  3. R01 AA023520/NIAAA NIH HHS
  4. R21 AA023035/NIAAA NIH HHS

MeSH Term

Animals
Brain
Disease Models, Animal
Ethanol
Female
Fetal Alcohol Spectrum Disorders
Pregnancy
Prenatal Exposure Delayed Effects
Proteome
Rats, Sprague-Dawley

Chemicals

Proteome
Ethanol
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 2

Word Cloud

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