title: Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in the mouse dentate gyrus.
abstract: Neurogenesis persists in certain regions of the adult brain including the subgranular zone of the hippocampal dentate gyrus wherein its regulation is essential, particularly in relation to learning, stress and modulation of mood. Lysophosphatidic acid (LPA) is an extracellular signaling phospholipid with important neural regulatory properties mediated by specific G protein-coupled receptors, LPA(1-5). LPA(1) is highly expressed in the developing neurogenic ventricular zone wherein it is required for normal embryonic neurogenesis, and, by extension may play a role in adult neurogenesis as well. By means of the analyses of a variant of the original LPA(1)-null mutant mouse, termed the Malaga variant or "maLPA(1)-null," which has recently been reported to have defective neurogenesis within the embryonic cerebral cortex, we report here a role for LPA(1) in adult hippocampal neurogenesis. Proliferation, differentiation and survival of newly formed neurons are defective in the absence of LPA(1) under normal conditions and following exposure to enriched environment and voluntary exercise. Furthermore, analysis of trophic factors in maLPA(1)-null mice demonstrated alterations in brain-derived neurotrophic factor and insulin growth factor 1 levels after enrichment and exercise. Morphological analyses of doublecortin positive cells revealed the anomalous prevalence of bipolar cells in the subgranular zone, supporting the operation of LPA(1) signaling pathways in normal proliferation, maturation and differentiation of neuronal precursors.
authors: Unidad de Investigación, Fundación IMABIS, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
authors: Elisa
authors: E
authors: Matas-Rico
authors: Beatriz
authors: B
authors: García-Diaz
authors: Pedro
authors: P
authors: Llebrez-Zayas
authors: Diana
authors: D
authors: López-Barroso
authors: Luis
authors: L
authors: Santín
authors: Carmen
authors: C
authors: Pedraza
authors: Anibal
authors: A
authors: Smith-Fernández
authors: Pedro
authors: P
authors: Fernández-Llebrez
authors: Teresa
authors: T
authors: Tellez
authors: Maximino
authors: M
authors: Redondo
authors: Jerold
authors: J
authors: Chun
authors: Fernando Rodríguez
authors: FR
authors: De Fonseca
authors: Guillermo
authors: G
authors: Estivill-Torrús
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011897:Random Allocation; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D049368:Receptors, Lysophosphatidic Acid