Chronic prenatal exposure to carbon monoxide results in a reduction in tyrosine hydroxylase-immunoreactivity and an increase in choline acetyltransferase-immunoreactivity in the fetal medulla: implications for Sudden Infant Death Syndrome

J Neuropathol Exp Neurol. 2000 Mar;59(3):218-28. doi: 10.1093/jnen/59.3.218.


Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in the fetal guinea pig. Pregnant guinea pigs were exposed to 200 p.p.m CO for 10 h per day from day 23-25 of gestation (term = 68 days) until day 61-63, at which time fetuses were removed and brains collected for analysis. Using immunohistochemistry and quantitative image analysis, examination of the medulla of CO-exposed fetuses revealed a significant decrease in tyrosine hydroxylase-immunoreactivity (TH-IR) in the nucleus tractus solitarius, dorsal motor nucleus of the vagus (DMV), area postrema, intermediate reticular nucleus, and the ventrolateral medulla (VLM), and a significant increase in choline acetyltransferase-immunoreactivity (ChAT-IR) in the DMV and hypoglossal nucleus compared with controls. There was no difference between groups in immunoreactivity for the m2 muscarinic acetylcholine receptor, substance P- or met-enkephalin in any of the medullary nuclei examined, nor was there evidence of reactive astrogliosis. The results show that prenatal exposure to CO affects cholinergic and catecholaminergic pathways in the medulla of the guinea pig fetus, particularly in cardiorespiratory centers, regions thought to be compromised in SIDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / chemistry
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Blotting, Western
  • Carbon Monoxide / adverse effects*
  • Choline O-Acetyltransferase / analysis
  • Choline O-Acetyltransferase / immunology
  • Choline O-Acetyltransferase / metabolism*
  • Enkephalin, Methionine / analysis
  • Enkephalin, Methionine / immunology
  • Female
  • Glial Fibrillary Acidic Protein / analysis
  • Glial Fibrillary Acidic Protein / immunology
  • Guinea Pigs
  • Medulla Oblongata / embryology
  • Medulla Oblongata / enzymology
  • Medulla Oblongata / pathology*
  • Neurons / chemistry
  • Neurons / drug effects
  • Neurons / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic / analysis
  • Receptors, Muscarinic / immunology
  • Smoking / adverse effects
  • Substance P / analysis
  • Substance P / immunology
  • Sudden Infant Death*
  • Tyrosine 3-Monooxygenase / analysis
  • Tyrosine 3-Monooxygenase / immunology
  • Tyrosine 3-Monooxygenase / metabolism*


  • Glial Fibrillary Acidic Protein
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic
  • Substance P
  • Enkephalin, Methionine
  • Carbon Monoxide
  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase