l-152804 and Neural-Tube-Defects

Gastrointestinal (GI) hormones play an important role in GI secretion, motility, and eating behaviors. It was recently suggested that GI hormones may have a trophic role in GI tract. Here we demonstrate that two principal GI hormones, anorexigenic peptide YY (PYY) and orexigenic ghrelin, affect neural tube development. Chronic administration into the pregnant mice or transgenic overexpression of PYY led to a neural tube defect (NTD) in the embryos that was blocked by ghrelin. PYY Y1 receptor antagonist prevented the occurrence of NTD induced not only by PYY but also by vitamin A, a well-known teratogen in humans and animals. Y1 receptor deficiency also engendered NTDs, indicating the need to maintain normal Y1 receptor signaling. The present study is the first linking GI hormones to the leading cause of infant mortality and provides a novel insight for neurogenesis in which materno-fetal communication through GI hormones appears to be important.

Topics: Animals; Arginine; Brain; Brain Chemistry; Cyclohexanes; Eating; Female; Folic Acid; Genes, Lethal; Genes, Synthetic; Ghrelin; Maternal-Fetal Exchange; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Mice, Transgenic; Neural Tube Defects; Neuropeptide Y; Pancreatic Polypeptide; Peptide Fragments; Peptide Hormones; Peptide YY; Pregnancy; Receptors, Neuropeptide Y; Recombinant Fusion Proteins; Teratogens; Vitamin A; Xanthenes