Qué sabemos sobre las consecuencias a largo plazo de la separación materna temprana y la respuesta neuroendocrina al estrés

Adverse conditions during early life are a risk factor for stress-related diseases. How this early adversity induce long-term effects is not well understood, however there are several evidence that the stress hormones play a determining role. Here we will focus on evidence obtained from the long-term consequences of prolonged maternal separation procedures. The purpose of this article is to review the literature about the influence of early experiences on the hypothalamic-pituitaryadrenal (HPA) axis function and endocrine stress responses in rodents. Early experiences have long-term influences on the behavioral and endocrine responses to stress and the alterations depend mostly on environment conditions and the interaction between mother and offspring. In the rodent, brief periods of separation result in an attenuated adrenal response to stress (reduced secretion of corticosterone). In contrast, longer periods of separation result in an exaggerated response. Besides, it is known that the prevalence of affective and anxiety disorders are significantly higher in women than in men. Emotional reactivity to stress and abnormalities in HPA axis activity have been implicated in the etiology of both depression and anxiety disorders. Therefore sexually dimorphic effects of maternal separation on the HPA axis function are discussed since gender is an important factor influencing the response to stress. The literature clearly demonstrates that early experiences trigger long-term changes in the stress system that may permanently alter brain and behaviour.Fil: Rivarola, María Angélica. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Renard, Georgina Maria. Universidad de Valparaíso; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Gender-dependent effects of early maternal separation and variable chronic stress on vasopressinergic activity and glucocorticoid receptor expression in adult rats

The aim of the present study was to investigate the influence of early maternal separation on Fos, arginine vasopressin (AVP) and glucocorticoid receptor (GR) expression in the medial parvocellular portion of the paraventricular hypothalamic nucleus (PaMP), and GR expression in the hippocampus of adult male and female rats subjected to variable chronic stress (VCS). Male and female Wistar rats were isolated 4.5 h daily, during the first 3 weeks of life. At 48 days of age, the rats were exposed to VCS. Nonmaternally separated (NMS) females had a higher number of activated AVP neurons than NMS male rats. Maternally separated (MS) females subjected to VCS also showed a higher number of Fos/AVP double-labeled neurons than males with the same treatment. Males and females subjected to early maternal separation and VCS, compared with the MS animals, showed a decrease in the expression of GR in the PaMP. As regards GR expression in the hippocampus, MS animals subjected to VCS as adults, both males and females, showed an increase in GR expression in the subfields CA1, CA2 and CA3. The increase in AVP-immunoreactive neurons coexpressing Fos in response to stress in females exposed to early maternal separation suggests that perhaps early life stress results in a more reactive neuroendocrine stress response in females. Furthermore, our results demonstrate that the different anatomical levels of the hypothalamic-pituitary-adrenal axis have different roles related to its stress response and support the evidence of regional specificity in GR regulation. Copyright © 2010 S. Karger AG, Basel.Fil: Renard, Georgina Maria. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivarola, María Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Suárez, M. M.. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología Animal; Argentin

Postweaning Enriched Environment Enhances Cognitive Function and Brain-Derived Neurotrophic Factor Signaling in the Hippocampus in Maternally Separated Rats

Adverse environments during early life may lead to different neurophysiological and behavioral consequences, including depression and learning and memory deficits that persist into adulthood. Previously, we demonstrated that exposure to an enriched environment during adolescence mitigates the cognitive impairment observed after maternal separation in a task-specific manner. However, underlying neural mechanisms are still not fully understood. The current study examines the effects of neonatal maternal separation (MS) and postweaning environmental enrichment (EE) on spatial learning and memory performance in a short version of the Barnes Maze, active and passive behaviors in the forced swim test, and on TrkB/BDNF receptor expression in the hippocampus. Our results revealed that MS impaired acquisition learning and that enriched rats performed better than non-enriched rats in acquisition trials, regardless of early conditions. During the probe, enriched-housed rats demonstrated better performance than those reared in standard conditions. No significant differences between groups were found in the forced swim test. Both MS and EE increase full-length TrkB expression, and the combination of MS and EE treatment caused the highest levels of this protein expression. Similarly, truncated TrkB expression was higher in the MS/EE group. Animal facility rearing (AFR) non-enriched groups present the lowest activation of phosphorylated Erk, a canonical downstream kinase of TrkB signaling. Taken together, our results demonstrate the importance of enriched environment as an intervention to ameliorate the effects of maternal separation on spatial learning and memory. TrkB/BDNF signaling could mediate neuroplastic changes related to learning and memory during exposure to enriched environment.Fil: Cordier, Javier Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; ArgentinaFil: Aguggia, Julieta Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Danelon, Víctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Mir, Franco Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Rioja; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología. Cátedra de Fisiología Animal; ArgentinaFil: Rivarola, María Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología. Cátedra de Fisiología Animal; ArgentinaFil: Masco, Daniel Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Consideraciones sobre la experimentación in vivo en Argentina. Aplicación a un caso particular: Implantes de titanio, titanio poroso y composite de titanio-hidroxiapatita

Trabajar con animales de experimentación para realizar ensayos de biocompatibilidad in vivo, requiere delcumplimiento de diversos protocolos. Además, usar animales para el estudio tiene una serie de implicancias de orden ético y legalque se deben tener en cuenta cuando se planifican las experiencias.En este trabajo se analizan los protocolos que hay que tener en cuenta en Argentina para la experimentación con animales delaboratorio. También se muestran, a modo de ejemplo, los resultados de ensayos in vivo de implantación de muestras de Ti (TiD),titanio poroso (TiP) y composite de titanio-hidroxiapatita (TiHA), obtenidos por proceso pulvimetalúrgico, en ratas de la cepaWistar. Los procedimientos desarrollados para la selección de los animales, proceso quirúrgico y control posquirúrgicoresultaron adecuados y se pudo comprobar buena adherencia del hueso con la superficie de los implantes y un inicio deformación de apatitas en los poros de los implantes porosos.Work with experimental animals to perform biocompatibility tests in vivo, requires compliance with various protocols. In addition, the use of animals for study has a number of ethical and legal implications that must be taken into account when planning experiences.In this paper we analyze the protocols that must be taken into account inArgentina for experimentation with laboratory animals. As an example, the results of in vivo implantation tests using Ti (TiD), porous titanium (TiP) and titanium-hydroxyapatite (TiHA) samples, obtained by the powder metallurgical process, in Wistar rats are also shown. The procedures developed for animal selection, surgical procedure and post-surgical control were adequate. Good adhesion of the bone to the surface of the implants could be verified and also a start of apatite formation in the pores of the porous implants.Fil: Suarez, Marta Magdalena. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Rivarola, María Angélica. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Grinschpun, Luciano. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Oldani, Carlos Rodolfo. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Maturana, Stefanía. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Bianchi, Santiago Julián. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Amietta, Joaquín. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Boezio, Lucía. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentin

Sex Differences in Anxiety and Depression: What Can (and Cannot) Preclinical Studies Tell Us?

In recent years, the gender perspective in scientific research and sex differences in biological studies on emotional disorders have become increasingly important. However, sex bias in basic research on anxiety and depression is still far from being covered. This review addresses the study of sex differences in the field of anxiety and depression using animal models that consider this issue so far. What can preclinical studies tell us and what are their main limitations? First, we describe the behavioral tests most frequently used in preclinical research to assess depressive-like and anxiety-like behaviors in rodents. Then, we analyze the main findings, strengths, and weaknesses of rodent models of anxiety and depression, dividing them into three main categories: sex chromosome complement-biased sex differences; gonadal hormone-biased sex differences; environmental-biased sex differences. Regardless of the animal model used, none can reproduce all the characteristics of such complex and multifactorial pathologies as anxiety and depressive disorders; however, each animal model contributes to elucidating the bases that underlie these disorders. The importance is highlighted of considering sex differences in the responses that emerge from each model

Sex Differences in Anxiety and Depression: What Can (and Cannot) Preclinical Studies Tell Us?

In recent years, the gender perspective in scientific research and sex differences in biological studies on emotional disorders have become increasingly important. However, sex bias in basic research on anxiety and depression is still far from being covered. This review addresses the study of sex differences in the field of anxiety and depression using animal models that consider this issue so far. What can preclinical studies tell us and what are their main limitations? First, we describe the behavioral tests most frequently used in preclinical research to assess depressive-like and anxiety-like behaviors in rodents. Then, we analyze the main findings, strengths, and weaknesses of rodent models of anxiety and depression, dividing them into three main categories: sex chromosome complement-biased sex differences; gonadal hormone-biased sex differences; environmental-biased sex differences. Regardless of the animal model used, none can reproduce all the characteristics of such complex and multifactorial pathologies as anxiety and depressive disorders; however, each animal model contributes to elucidating the bases that underlie these disorders. The importance is highlighted of considering sex differences in the responses that emerge from each model.Fil: Mir, Franco Rafael. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología. Cátedra de Fisiología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivarola, María Angélica. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología. Cátedra de Fisiología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentin

Early maternal separation: Neurobehavioral consequences in mother rats

Repeated separation of dams from their pups during the postpartum period may evoke emotional stress in the dam. In the present study we investigated whether prolonged maternal separation is stressful for rat dams by studying different behavioral and central responses known to be affected by stress. After delivery, female Wistar rats were subjected to either animal facility rearing (AFR) conditions or daily 4.5 h of mother–litter separation from postpartum day (PPD) 1–21. Maternal care (pup retrieval) was evaluated at PPD 3. After weaning on PPD 21, anxiety (elevated plus maze) and depression-like behaviors (forced swimming test) were assessed in the dams. Memory abilities (one-trial step down inhibitory avoidance) were tested either 1 h (short-term memory) or 24 h (long-term memory) after training session. Finally, c-Fos expression was examined in the central nucleus of the amygdala. The results revealed that pup retrieval efficiency at PPD 3 was significantly impaired by maternal separation. AFR dams retrieved their pups sooner and engaged in more pup-directed activities (nest building and carrying pups). Separation from pups increased the number of entries in open arms of the plus maze and decreased latency times in the inhibitory avoidance test for both short and long-term memory in the dams. There were no differences in depression-related behavior as assessed using the forced swimming test. Furthermore, maternal separation yielded high c-Fos expression in the central nucleus of the amygdala. Together, these data indicate that repeated maternal separation in the early postpartum period reduces maternal care and impairs the retention memory, providing further evidence for the detrimental neurobehavioral effects of maternal separation in dams.Fil: Aguggia, Julieta Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Suarez, Marta Magdalena. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivarola, María Angélica. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Neurobiological effects of neonatal maternal separation and post-weaning environmental enrichment

Throughout the lifespan, the brain has a considerable degree of plasticity and can be strongly influenced by sensory input from the outside environment. Given the importance of the environment in the regulation of the brain structure, behavior and physiology, the aim of the present work was to analyze the effects of different environmental qualities during two critical ontogenic periods (early life and peripuberty) on behavior and hippocampal physiology.Male Wistar rats were separated from their mothers for 4.5. h daily during the first 3 weeks of life. They were weaned on day 21 and housed under either standard or enriched conditions. At 60 d of age, all animals were then housed in same-treatment groups, two per cage, until testing began on day 74. Emotional and cognitive responses were tested using the open field, novel object recognition test and step-down inhibitory avoidance learning. In the dorsal hippocampus, glucocorticoid receptor expression and neuronal activity were examined by immunoreactivity.Grooming behavior in the open field was found to be significantly lower in maternally separated animals, but post-weaning environmental enrichment completely reversed this tendency. Inhibitory avoidance but not object recognition memory was impaired in maternally separated animals, suggesting that early maternal separation alters learning and memory in a task-specific manner. Again, environmental enrichment reversed the effects of maternal separation on the inhibitory avoidance task. Even though maternal separation did not significantly affect Fos and glucocorticoid receptor (GR) expression, environmental enrichment increased both Fos expression in the total hippocampal area and also the overall number of GR positive cells per hippocampal area, mainly due to the changes in CA1.These findings suggest that differential rearing is a useful procedure to study behavioral and physiological plasticity in response to early experience and that, although the effects of adverse experience early in life such as maternal separation can persist until adulthood, some of them can be compensated by early favorable environments, possibly through nervous system plasticity.Fil: Vivinetto, Ana Laura. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Suarez, Marta Magdalena. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología Animal; ArgentinaFil: Rivarola, María Angélica. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentin

Parental enriched environment: A look through key temporary windows

Environmental enrichment is a widely used experimental manipulation that physically, cognitively and socially stimulates individuals. It has a great variety of long-term effects at neuroanatomical, neurochemical, and behavioral level; however, the influence of parental environmental enrichment during gestation and pregestation on the development of the offspring and on the mother's behavior has been poorly explored. This article presents a review of the literature from the year 2000 about the effects of maternal and paternal environmental enrichment on the behavioral, endocrine, and neural systems of offspring and parents. Relevant research terms were searched for on the biomedical databases, PubMed, Medline, ScienceDirect, and Google Scholar. The data suggest that paternal/maternal environmental enrichment can profoundly affect the developmental trajectories of offspring through putative epigenetic mechanisms. Environmental enrichment presents as a promising therapeutic tool for human health interventions, especially to counteract the deleterious effects of impoverished and adverse growing conditions.Fil: Mir, Franco Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología. Cátedra de Fisiología Animal; Argentina. Universidad Nacional de La Rioja; ArgentinaFil: Renard, Georgina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Santiago de Chile; ChileFil: Rivarola, María Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología. Cátedra de Fisiología Animal; Argentin

Multiparity dampened the behavioral consequences of mother-pup separation stress in dams

Reproductive experience in mammals produces significant neuroendocrine and behavioral changes that are necessary to ensure the survival of the mother and the young. Exposure to stress during postpartum may affect the proper development of maternal behaviors. The present study examined whether previous reproductive experience affects neurobehavioral responses in females exposed to mother–infant separation stress during the postpartum period (4.5 h/day for 3 weeks). Anxiety-like behavior and spatial learning were evaluated in nulliparous (NP), primiparous (PRI) and multiparous (MULT). In maternal animals (PRI and MULT), maternal behavior was also assessed. Cell survival and proliferation in the dentate gyrus, as well as BDNF expression in the hippocampus, were evaluated by immunohistochemistry as possible candidates for mediating brain plasticity in response to reproductive experience and stress. Anxiety-like behavior as measured on the open field test showed an increase in NP and PRI-stressed, while neither stressed nor unstressed MULT expressed this behavior. Maternal unstressed animals both PRI and MULT exhibited enhanced memory task performance in the Barnes maze. Multiparity increased cell proliferation and cell survival in female rats and these changes occurred independently of pup exposure. The expression of BDNF was higher in the CA1 area in MULT rats. Although multiparity protects the mother against some of the effects of maternal separation stress, promoting behaviors directed to the pups during the early postpartum, preventing anxiety-like behaviors and mitigating memory deterioration after weaning, the data showed that disrupting natural dam–pup interaction produced neurobiological consequences on the mother even with multiple reproductive experience.Fil: Aguggia, Julieta Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Suarez, Marta Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Rivarola, María Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentin