title: Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors: Departamento de Psicobiología y Metodología de las CC, Universidad de Málaga, Campus de Teatinos, Málaga, Spain.
authors: Estela
authors: E
authors: Castilla-Ortega
authors: Carolina
authors: C
authors: Hoyo-Becerra
authors: Carmen
authors: C
authors: Pedraza
authors: Jerold
authors: J
authors: Chun
authors: Fernando
authors: F
authors: Rodríguez De Fonseca
authors: Guillermo
authors: G
authors: Estivill-Torrús
authors: Luis J
authors: LJ
authors: Santín
mesh_terms: D000818:Animals; D001007:Anxiety / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017209:Apoptosis / Q000235:genetics; D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D000089622:Doublecortin Domain Proteins; D005106:Exploratory Behavior / Q000502:physiology; D055786:Gene Knockout Techniques; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000473:pathology; D055495:Neurogenesis; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D009929:Organ Size / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid / Q000172:deficiency* / Q000235:genetics*; D012149:Restraint, Physical / Q000009:adverse effects; D013037:Spatial Behavior / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D049368:Receptors, Lysophosphatidic Acid