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oai:repisalud.isciii.es:20.500.12105/170172024-11-28T14:44:23Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Castilla-Ortega, Estela author Hoyo-Becerra, Carolina author Pedraza, Carmen author Chun, Jerold author Rodríguez De Fonseca, Fernando author Estivill-Torrús, Guillermo author Santín, Luis J authoraffiliation [Castilla-Ortega, E; Pedraza, C; Santín, LJ] Departamento de Psicobiología y Metodología de las CC, Universidad de Málaga, Málaga, Spain. [Hoyo-Becerra, C; Rodríguez de Fonseca, F; Estibill-Torrús, G] Unidad de Investigación, Fundación IMABIS, Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Chun, J] Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, United States of America. 2024-01-15T17:54:05Z 2024-01-15T17:54:05Z 2011-09-29 10.1371/journal.pone.0025522 1932-6203 PloS one http://hdl.handle.net/10668/698 21980482 http://hdl.handle.net/20.500.12105/17017 BACKGROUND: The 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 FINDINGS: Male 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/SIGNIFICANCE: These 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. eng Animales Ansiedad recuento de células proliferación celular Supervivencia Celular Conducta Exploratoria técnicas de inactivación genética Hipocampo Masculino Memoria Ratones proteínas asociadas a microtúbulos células madre nerviosas Neurogénesis Neuronas Neuroglía tamaño de los órganos receptores de ácidos lisofosfatídicos restricción física Conducta Espacial Estrés Psicológico Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice. research article