title: Active coping of prenatally stressed rats in the forced swimming test: involvement of the Nurr1 gene.
abstract: Depending on genetic predisposition, prenatal stress may result in vulnerability or resilience to develop psychiatric disorders in adulthood. Nurr1 is an immediate early gene, important in the brain for the stress response. We tested the hypothesis that prenatal stress and the decrease of hippocampal Nurr1 alter offspring behavioral responses in the forced swimming test (FST). Pregnant Wistar rats were exposed to restraint stress (45 min, thrice daily) from gestation day 14. Prenatally stressed (PS) and non-prenatally stressed (NPS) male offspring were treated bilaterally with a Nurr1 antisense oligodeoxynucleotide (ODN; or control) into the hippocampus at 97 d of age. After 1 h, the rats were exposed to the FST (acute stressor) to analyze their behavioral responses. Thirty minutes after the FST, we analyzed the gene expression of Nurr1, Bdnf and Nr3c1 (genes for Nurr1, brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR), respectively) in the hippocampus, prefrontal cortex (PFC) and hypothalamus. Results showed that the decrease of hippocampal Nurr1 after the antisense ODN in adult NPS rats induces immobility (indicating depressive-like behavior). The PS adult rats, including the group with decreased hippocampal Nurr1, presented low immobility in the FST. This low immobility was concordant with maintenance of Nurr1 and Bdnf expression levels in the three analyzed brain regions; Nr3c1 gene expression was also maintained in the PFC and hypothalamus. These findings suggest that Nurr1 and associated genes could participate in the brain modifications induced by prenatal stress, allowing active coping (resilience) with acute stress in adulthood.
authors.affiliation: a Laboratory of Neurotoxicology , National Institute of Neurology and Neurosurgery, "Manuel Velasco Suárez" , Mexico D.F. , Mexico ;
authors.forename: Pedro
authors.initials: P
authors.lastname: Montes
authors.affiliation: a Laboratory of Neurotoxicology , National Institute of Neurology and Neurosurgery, "Manuel Velasco Suárez" , Mexico D.F. , Mexico ;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ruiz-Sánchez
authors.affiliation: b Experimental Laboratory of Neurodegenerative Diseases , National Institute of Neurology and Neurosurgery, "Manuel Velasco Suárez" , Mexico D.F. , Mexico.
authors.forename: Minerva
authors.initials: M
authors.lastname: Calvillo
authors.affiliation: a Laboratory of Neurotoxicology , National Institute of Neurology and Neurosurgery, "Manuel Velasco Suárez" , Mexico D.F. , Mexico ;
authors.forename: Patricia
authors.initials: P
authors.lastname: Rojas
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D013550:Swimming / Q000523:psychology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D011965:Receptors, Glucocorticoid
keywords: Corticosterone; depression-like behavior; gestational stress; hippocampus; nuclear receptor; stress resilience