title: Lysophosphatidic acid signaling may initiate fetal hydrocephalus.
abstract: Fetal hydrocephalus (FH), characterized by the accumulation of cerebrospinal fluid, an enlarged head, and neurological dysfunction, is one of the most common neurological disorders of newborns. Although the etiology of FH remains unclear, it is associated with intracranial hemorrhage. Here, we report that lysophosphatidic acid (LPA), a blood-borne lipid that activates signaling through heterotrimeric guanosine 5'-triphosphate-binding protein (G protein)-coupled receptors, provides a molecular explanation for FH associated with hemorrhage. A mouse model of intracranial hemorrhage in which the brains of mouse embryos were exposed to blood or LPA resulted in development of FH. FH development was dependent on the expression of the LPA(1) receptor by neural progenitor cells. Administration of an LPA(1) receptor antagonist blocked development of FH. These findings implicate the LPA signaling pathway in the etiology of FH and suggest new potential targets for developing new treatments for FH.
authors: Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: Yun C
authors: YC
authors: Yung
authors: Tetsuji
authors: T
authors: Mutoh
authors: Mu-En
authors: ME
authors: Lin
authors: Kyoko
authors: K
authors: Noguchi
authors: Richard R
authors: RR
authors: Rivera
authors: Ji Woong
authors: JW
authors: Choi
authors: Marcy A
authors: MA
authors: Kingsbury
authors: Jerold
authors: J
authors: Chun
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D005333:Fetus / Q000033:anatomy & histology / Q000473:pathology; D006801:Humans; D006849:Hydrocephalus / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007231:Infant, Newborn; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D010949:Plasma / Q000378:metabolism; D011247:Pregnancy; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; C032881:lysophosphatidic acid