PloS one, 2015-02, Vol.10 (2), p.e0117680
2015
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- Autor(en) / Beteiligte
- Titel
- Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats
- Ist Teil von
- PloS one, 2015-02, Vol.10 (2), p.e0117680
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that can yield new insights on the molecular mechanisms behind the effects of prenatal stress.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0117680Titel-ID: cdi_plos_journals_1656698881
- Format
- –
- Schlagworte
- Adults, Animal cognition, Animals, Animals, Newborn, Antigens, Nuclear - genetics, Antigens, Nuclear - metabolism, Anxiety, Behavior, Behavior, Animal, Biology, Biomedical research, Brain, Brain research, Cell Adhesion Molecules, Neuronal - genetics, Cell Adhesion Molecules, Neuronal - metabolism, Cell culture, Cells (Biology), Cerebral Cortex - metabolism, Cognitive ability, Cortex, Cyclin-Dependent Kinase 5 - metabolism, Deoxyribonucleic acid, Deregulation, Disease Models, Animal, DNA, DNA Methylation, Epigenetics, Exposure, Extracellular Matrix Proteins - genetics, Extracellular Matrix Proteins - metabolism, Female, Females, Fetuses, Gender differences, Genomes, Kinases, Laboratories, Lamination, Learning, Locomotor activity, Maternal Exposure, Memory, Memory tasks, Mental depression, Mental disorders, Mental Disorders - etiology, Methylation, Molecular biology, Molecular chains, Molecular modelling, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Neurons, Neurons - metabolism, Pregnancy, Prenatal development, Prenatal experience, Prenatal Exposure Delayed Effects, Promoter Regions, Genetic, Proteins, Rats, Reelin protein, Risk factors, Rodents, Schizophrenia, Serine Endopeptidases - genetics, Serine Endopeptidases - metabolism, Signal Transduction, Signaling, Spatial analysis, Spatial memory, Stress, Stress, Physiological, Stress, Psychological, Stresses