Document Detail

Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in the mouse dentate gyrus.
MedLine Citation:
PMID:  18708146     Owner:  NLM     Status:  MEDLINE    
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.
Elisa Matas-Rico; Beatriz García-Diaz; Pedro Llebrez-Zayas; Diana López-Barroso; Luis Santín; Carmen Pedraza; Anibal Smith-Fernández; Pedro Fernández-Llebrez; Teresa Tellez; Maximino Redondo; Jerold Chun; Fernando Rodríguez De Fonseca; Guillermo Estivill-Torrús
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-07-29
Journal Detail:
Title:  Molecular and cellular neurosciences     Volume:  39     ISSN:  1095-9327     ISO Abbreviation:  Mol. Cell. Neurosci.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-22     Completed Date:  2009-01-29     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9100095     Medline TA:  Mol Cell Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  342-55     Citation Subset:  IM    
Unidad de Investigación, Fundación IMABIS, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
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MeSH Terms
Apoptosis / physiology
Behavior, Animal / physiology
Biological Markers / metabolism
Dentate Gyrus / cytology,  physiology*
Gene Deletion*
Mice, Inbred C57BL
Mice, Knockout
Neurogenesis / physiology*
Neuronal Plasticity / physiology
Neurons / cytology,  physiology
Random Allocation
Receptors, Lysophosphatidic Acid* / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Biological Markers; 0/Receptors, Lysophosphatidic Acid

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