title: Impaired brain development and reduced cognitive function in phospholipase D-deficient mice.
abstract: The phospholipases D (PLD1 and 2) are signaling enzymes that catalyze the hydrolysis of phosphatidylcholine to phosphatidic acid, a lipid second messenger involved in cell proliferation, and choline, a precursor of acetylcholine (ACh). In the present study, we investigated development and cognitive function in mice that were deficient for PLD1, or PLD2, or both. We found that PLD-deficient mice had reduced brain growth at 14-27 days post partum when compared to wild-type mice. In adult PLD-deficient mice, cognitive function was impaired in social and object recognition tasks. Using brain microdialysis, we found that wild-type mice responded with a 4-fold increase of hippocampal ACh release upon behavioral stimulation in the open field, while PLD-deficient mice released significantly less ACh. These results may be relevant for cognitive dysfunctions observed in fetal alcohol syndrome and in Alzheimer' disease.
authors.affiliation: Department of Pharmacology, Goethe University College of Pharmacy, Frankfurt, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Burkhardt
authors.affiliation: Vascular Medicine, University Hospital Würzburg & Rudolf Virchow Center, University of Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Stegner
authors.affiliation: Institute of Neuroradiology, Goethe University Medical Center, Frankfurt, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hattingen
authors.affiliation: Department of Pharmacology, Goethe University College of Pharmacy, Frankfurt, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Beyer
authors.affiliation: Vascular Medicine, University Hospital Würzburg & Rudolf Virchow Center, University of Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: Department of Pharmacology, Goethe University College of Pharmacy, Frankfurt, Germany. Electronic address: Klein@em.uni-frankfurt.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Klein
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000473:pathology*; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism; D018345:Mice, Knockout; D010739:Phospholipase D / Q000235:genetics*
chemical_list: C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1; D000109:Acetylcholine
keywords: Acetylcholine; Alzheimer’ disease; Brain growth spurt; Fetal alcohol syndrome; Microdialysis; Phospholipase D