RT Journal Article
T1 Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice.
A1 Castilla-Ortega, Estela
A1 Hoyo-Becerra, Carolina
A1 Pedraza, Carmen
A1 Chun, Jerold
A1 Rodríguez de Fonseca, Fernando
A1 Estivill-Torrús, Guillermo
A1 Santín, Luis J
K1 Animales
K1 Ansiedad
K1 recuento de células
K1 proliferación celular
K1 Supervivencia Celular
K1 Conducta Exploratoria
K1 técnicas de inactivación genética
K1 Hipocampo
K1 Masculino
K1 Memoria
K1 Ratones
K1 proteínas asociadas a microtúbulos
K1 células madre nerviosas
K1 Neurogénesis
K1 Neuronas
K1 Neuroglía
K1 tamaño de los órganos
K1 receptores de ácidos lisofosfatídicos
K1 restricción física
K1 Conducta Espacial
K1 Estrés Psicológico
AB BACKGROUNDThe lysophosphatidic acid LPA₁ receptor regulates plasticity and neurogenesis in the adult hippocampus. Here, we studied whether absence of the LPA₁ receptor modulated the detrimental effects of chronic stress on hippocampal neurogenesis and spatial memory.METHODOLOGY/PRINCIPAL FINDINGSMale LPA₁-null (NULL) and wild-type (WT) mice were assigned to control or chronic stress 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 structure and apoptosis in the hippocampus. Corticosterone levels were measured in another a separate cohort of mice. Finally, the hole-board test assessed spatial reference and working memory. Under control conditions, NULL mice showed reduced cell proliferation, a defective population of young neurons, reduced hippocampal volume and moderate spatial memory deficits. However, the primary result is that chronic stress impaired hippocampal neurogenesis in NULLs more severely than in WT mice in terms of cell proliferation; apoptosis; the number and maturation of young neurons; and both the volume and neuronal density in the granular zone. Only stressed NULLs presented hypocortisolemia. Moreover, a dramatic deficit in spatial reference memory consolidation was observed in chronically stressed NULL mice, which was in contrast to the minor effect observed in stressed WT mice.CONCLUSIONS/SIGNIFICANCEThese results reveal that the absence of the LPA₁ receptor aggravates the chronic stress-induced impairment to hippocampal neurogenesis and its dependent functions. Thus, modulation of the LPA₁ receptor pathway may be of interest with respect to the treatment of stress-induced hippocampal pathology.
PB Public Library of Science
YR 2011
FD 2011-09-29
LK http://hdl.handle.net/10668/698
UL http://hdl.handle.net/10668/698
LA en
NO Castilla-Ortega E, Hoyo-Becerra C, Pedraza C, Chun J, Rodríguez De Fonseca F, Estivill-Torrús G, et al. Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice. PLoS ONE 2011; 6(9):e25522
NO Formal Correction: Error in FundingPosted by PLoS_ONE_Group on 29 Nov 2011 at 22:27 GMT The complete funding information is: "This work was supported by grants from the Spanish Ministry of Education and Science (MEC SEJ2007-61187, MICINN PSI2010-16160 to LJS), Programme for Stabilization of Researchers and Research Technician and Intensification of Research Activity in the National Health System (I3SNS Programme to GET), the Human Frontier Science Programme (to JC, FRDF), Fund for Health Research, Carlos III Health Institute (FIS 02/1643, FIS PI07/0629, FIS PI10/02514 to GET), Red de Trastornos Adictivos RTA (RD06/001 to FRDF), Andalusian Ministry of Health and of Innovation, Science and Enterprise (CTS065 to GET; CTS433 to FRDF) and the US National Institutes of Health MH051699 and MH01723 (to JC). The author E. Castilla-Ortega has a FPU Grant from the Spanish Ministry of Education (AP-2006-02582). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript." Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 18, 2025