Aggravation of Chronic Stress Effects on Hippocampal Neurogenesis and Spatial Memory in LPA1 Receptor Knockout Mice 英文参考文献.docVIP

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Aggravation of Chronic Stress Effects on Hippocampal Neurogenesis and Spatial Memory in LPA1 Receptor Knockout Mice 英文参考文献.doc

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Aggravation of Chronic Stress Effects on Hippocampal Neurogenesis and Spatial Memory in LPA1 Receptor Knockout Mice 英文参考文献

AggravationofChronicStressEffectsonHippocampal NeurogenesisandSpatialMemoryinLPA1Receptor KnockoutMice EstelaCastilla-Ortega1,CarolinaHoyo-Becerra2,CarmenPedraza1,JeroldChun3,FernandoRodr?′guez DeFonseca2,GuillermoEstivill-Torru′s2,LuisJ.Sant?′n1* 1DepartamentodePsicobiolog?′ayMetodolog?′adelasCC,UniversidaddeMa′laga, CampusdeTeatinos,Ma′laga, Spain,2UnidaddeInvestigacio′n,Fundacio′nIMABIS, Hospital Regional Universitario Carlos Haya, Ma′laga, Spain, 3Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California,UnitedStatesofAmerica Abstract Background: The lysophosphatidic acid LPA1 receptor regulates plasticity and neurogenesis in the adult hippocampus. Here,westudiedwhetherabsenceoftheLPA1receptormodulatedthedetrimentaleffectsofchronicstressonhippocampal neurogenesisandspatialmemory. Methodology/PrincipalFindings:MaleLPA1-null(NULL)andwild-type(WT)micewereassignedtocontrolorchronicstress conditions (21 days of restraint, 3 h/day). Immunohistochemistry for bromodeoxyuridine and endogenous markers was performed to examine hippocampal cell proliferation, survival, number and maturation of young neurons, hippocampal structureandapoptosisinthehippocampus.Corticosteronelevelsweremeasuredinanotheraseparatecohortofmice. Finally,thehole-boardtestassessedspatialreferenceandworkingmemory.Undercontrolconditions,NULLmiceshowed reducedcellproliferation,adefectivepopulationofyoungneurons,reducedhippocampalvolumeandmoderatespatial memory deficits. However, the primary result is that chronic stress impaired hippocampal neurogenesis in NULLs more severelythaninWTmiceintermsofcellproliferation;apoptosis;thenumberandmaturationofyoungneurons;andboth the volume and neuronal density in the granular zone. Only stressed NULLs presented hypocortisolemia. Moreover, a dramaticdeficitinspatialreferencememoryconsolidationwasobservedinchronicallystressedNULLmice,whichwasin contrasttotheminoreffectobservedinstressedWTmice. Conclusion