Maternal separation on postnatal stress in rats induces long-lasting changes on neurochemical, behavioural and genome responses

Early stress in life results in long-lasting effects in many neurotransmitter and neuroendocrine systems of the brain. Maternal separation (MS) is used an early life stressor that causes profound neurochemical and behavioural changes in the pups that persist into adulthood. Manipulations such as prolonged MS of pups from the dam have been used as an animal model of early-life trauma. Animal models are quite useful for elucidating the mechanisms underlying abnormalities toward possible treatment strategies for psychiatric, emotional or neurological diseases. The central nervous system (CNS) maintains a degree of adaptive plasticity, which allows adjusting to certain circumstances and modifying innate patterns from neuronal connections. Alterations during development, such as postnatal stress, provoke changes in the stress response of the pups during their whole lives. It is believed that the effects of these events during early life are due to the great plasticity of the developing in CNS. Along the critical period of certain brain regions, mainly, those related to adverse situations, for example frontal cortex, hippocampus, and hypothalamic-pituitary-adrenal (HPA) axis can develop abnormalities sometimes irreversible and thus alter the emotional process and the stress response along the animal?s life. Early postnatal period and bond between mother and infant seem particularly important in the development and shaping of normal stress response and emotional behavior. Epigenetic modifications, such as DNA methylation, are critical regulators of persistent gene expression changes and may be related to behavioural disorders. However the mechanisms underlying the long-term effects of environmental stress early in life are not known, they are likely to involve activation of intracellular signalling pathways, leading to modifications of the genome, resulting in changes in gene expression and neural function. The neural modifies underlying the persistent effects of early life separation and stress in rodents remain to be fully elucidated.Fil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentin

Mysteries and realities of Alzheimer`s disease

En este artículo se presenta la complejidad de la enfermedad de Alzheimer (EA), cuya principal causa es la demencia entre los adultos mayores y está siendo estudiada firmemente para que en un futuro no muy lejano se desarrollen nuevos blancos terapéuticos en el tratamiento de la misma. Se desconoce su etiología, no es parte del proceso de envejecimiento normal, es la forma más común de demencia, es incurable y terminal, aparece con mayor frecuencia en personas mayores de 65 años de edad. Los mecanismos patológicos involucrados en ella son: la formación del péptido β-amiloide, la aparición de placas seniles, alteraciones en la proteína tau, la formación de ovillos neurofibrilares, la aparición de una cascada inflamatoria, el daño oxidativo neuronal, el mal funcionamiento sináptico y el agotamiento de neurotransmisores especialmente de acetilcolina. Varios de estos eventos son comunes a muchos trastornos neurodegenerativos progresivos. Las formas familiares secundarias de la enfermedad de Alzheimer, pueden ser mutaciones hereditarias que proporcionan una visión más amplia de los mecanismos moleculares implicados en la patogénesis de la enfermedad. Las causas que subyacen a la EA así como su tratamiento se encuentran en estudio. Una serie de valiosas herramientas terapéuticas y de diagnóstico se están desarrollado actualmente. Los factores de riesgo para la EA son la edad, la predisposición genética, los factores ambientales, las enfermedades cardiovasculares, la diabetes y la dieta. En estos últimos años, la EA ha cobrado un relieve significativo, no sólo en el ámbito médico, sino también, en la comunidad en general. La EA tiene un curso devastador para el paciente y su familia, con un costo económico-social que aumenta en forma alarmante a medida que aumenta el porcentaje de la población geriátrica en la sociedad contemporánea. Palabras claves: Proteína β-amiloide, muerte celular, ovillos neurofibrilares, placas neuríticas, daño oxidativo, neurodegeneración, pérdida de memoria, predisposición genética, biomarcadores, impacto social, AlzheimerThis article present the complexity of Alzheimer's disease (AD) improves, the biological bases underlying its pathogenesis are gradually being disclosed, and we can expect that new therapeutic targets will emerge. In it is characterized behaviorally by progressive memory loss and cognitive decline and physiologically by the presence of beta-amyloid peptide (Aβ and neurofibrillary tangles) in the brain. The aim is to prevent or at least slow down the progression towards clinical impairment. The pathological mechanisms implicated the actions of β-amyloid, the accumulation of aggregates, the inflammatory cascade, oxidative neuronal damage, tau protein alterations and the formation of neurofibrillary tangle, synaptic failure and neurotransmitter depletion. Several of these events are common to many slowly progressive neurodegenerative disorders. The familial forms of Alzheimer’s, secondary to inherited mutations have provided an insight into the molecular mechanisms implicated in disease pathogenesis. The underlying cause of AD, as well as its treatment, is still under investigation. A number of valuable diagnostic tools have been developed and continue to be improved. Risk factors for AD include age, genetic predisposition, environmental factors, cardiovascular diseases, diabetes and diet.Fil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentin

Early Life Experience, Maternal Separation, and Involvement of GABA and Glutamate Transporters

The physiological response initiates with activation of the hypothalamic-pituitary-adrenal axis, the autonomic nervous, and the immune systems. All actions promoted cellular adaptive changes in cells and tissues that protect the body and promote their survival. Diverse protocols of maternal separation (MS) in rodents presented alterations in central nervous system (CNS) such as learning disabilities, voluntary alcohol intake, and neurochemical changes. It is believed that the properties of these early life procedures are mediated by the high plasticity of the developing CNS. During critical development stage, brain regions, mainly those related to aggressive conditions, can have advancement abnormalities occasionally irreversible and thus adjust emotional processing when they grow to be adults. Early postnatal period and relationship between mother and infant are essential of normal stress response and emotional behavior. Probably, it involves the activation of intracellular signaling pathways, genome adaptations, adjusts in gene expression, and neural action. The objective of this article is to provide an overview of the current state of knowledge in the field focused on the maternal separation model, early life experience of postnatal stress, and the involvement of γ-aminobutyric acid (GABA) and glutamate transporters

Consequences of postnatal stress: maternal separation in rats induces long-lasting changes on glutamate transporters

Background: There is increasing evidence that environmental factors, particularly stressful events experienced early in life, increase the risk of developing a psychiatric illness and/or a behavioural disorder. The aim of this study was to evaluate the effects of acute and chronic maternal separation (AMS and CMS) plus cold stress on the expression patterns of Glutamate Transporters (TGlus) in the developing and young adult Central Nervous System (CNS). As regulation of Glutamate (Glu) extracellular levels is of key importance, sodium-dependent Glu uptake using synaptosome-enriched fractions isolated from Frontal Cortex (FC) and Hippocampus (Hic) was also studied. Results: In animals under AMS stress found that Glu uptake decreases with respect to control groups. Meanwhile in CMS did not observe changes on Glu uptake in adult animals. These data would suggest the existence of an adaptive mechanism that could compensate the effect of AMS and CMS plus cold stress on glutamate uptake. Western blotting was performed in homogenates prepared from FC and Hic from both neonate and young adult rat brains. These blots exposed that homogenates include GLT-1 and EAAC-1 proteins and their levels varied in different areas of the rat brain and with the age of animals. Conclusions: During early postnatal life, exposure to various stressors lead to the development of various neurological, psychiatric, neurodegenerative and behavioral disorders, expressible in adult life in the case of chronic stress. These results demonstrate that adverse early life events have profound and persistent effects on brain function and may represent a risk factor for the development of psychopathology later life.Fil: Odeon, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Salatino, Adrián Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentin

Gabapentin, an antiepileptic drug, improves memory storage in mice

Male CF-1 mice were tested 48 h after training in a one-trial step- through inhibitory avoidance task. Immediately post-training i.p. injections of the antiepileptic drug gabapentin (1-aminomethyl cyclohexaneacetic acid) (GBP; 5, 10, 50, and 100 mg/kg) induced a dose-dependent enhancement of retention performance. Gabapentin did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of GBP on retention were not due to non-specific proactive effects on response latencies. The effects of GBP (10 mg/kg) were time-dependent, and the administration of GBP (10 mg/kg) 30 min before training also enhanced retention performance. However, the administration of GBP (10 mg/kg) 30 min prior to the retention test did not modify retention latencies of mice that had received either saline or GBP (10 mg/kg) immediately after training. Altogether, the results suggest that GBP influences retention by modulating time-dependent processes involved in memory storage, although the mechanism(s) of this action remain to be established. (C) 2000 Elsevier Science Ireland Ltd.Fil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Boccia, Mariano Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Baratti, Carlos Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentin

Prenatal Stress and its effects of human cognition, behavior and psychopathology: A review of the literature

Stress plays a fundamental role in the etiology and evolution of diseases and disorders both in the early stages of development and the adult life. Neuropsychiatric disorders such as depression, autism, ADHD and schizophrenia have a complex etiology, which is influenced by early experiences that affect the vulnerability of the individual.During early intrauterine and postnatal life, the developing organism undergoes complex physiological changes, and even small disturbances can have far-reaching consequences which can be observed even into adulthood. Currently, understanding the factors that may be affecting the organism during development is a challenge. Among the effects induced by Prenatal Stress we can mention a dysregulation of the HPA axis, an alteration of the circadian rhythm, a reduction of the hippocampal plasticity and the capacity of learning and memory among others.The effects of Prenatal Stress are widely studied in laboratory animals, but systematic research on human subjects is comparatively scarce. While studies in humans suffer from certain methodological limitations, they are currently the only way to explore some of the most complex, long-term interactions between antenatal stress and the behavioral and cognitive alterations of the offspring. This work aims to review studies about Prenatal Stress pertaining human subjects, and to explore some of the controversies arising on this field.Fil: Ramborger, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Zorrilla Zubilete, María Aurelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentin

Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats

Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of alcohol voluntary intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, the pups were separated from their mothers and exposed to cold stress (4ºC) for 1h during 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: 1) increased voluntary ethanol intake; 2) did not affect body weight gain or produce signs of toxicity with alcohol exposure; 3) increased glutamate uptake by hippocampal synaptosomes in vitro 4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to put a stop to enlarged extracellular glutamate levels is inferred. The results also demonstrate that CPS strongly increased intake of ethanol, which had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.Fil: Odeon, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Andreu, Marcela. Laboratorio Bioquímica Médica; ArgentinaFil: Yamauchi, Laura. Laboratorio Bioquímica Médica; ArgentinaFil: Grosman, Mauricio. Laboratorio Bioquímica Médica; ArgentinaFil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Influencia del programa socio bosque en la dinámica de los servicios ambientales de los bosques secos deciduos del Ecuador

This paper analyzes the influence of “Programa Socio Bosque” in the dynamics of Environmental Services of Dry Deciduous Forests of Ecuador. These forests are formations under the warm plains of the Ecuadorian coast, have the characteristic of losing 75% of their leaves during the dry season. An area of 467.210,89 hectares of Dry Deciduous Forest, spread throughout the provinces of Manabí, Guayas, Santa Elena, El Oro and Loja are currently registered. Since 2008, the Ministry of Environment of Ecuador, implements a policy of incentives for the conservation of native forests, participants or partners in this program are committed to conservation areas in return receive an economic incentive per hectare conserved. Within the study, was identified a potential area of analysis corresponds to 372.492,77 hectares, these spaces were compared using a multitemporal study in three periods (1990-2000), (2001-2008) and (2009.2012), identifying changes in coverage vegetation and land use in the catchment area of dry deciduous forests. The results of multitemporal study show a change in the following classes: Native Forests have a trend of decreasing surface basically effects of deforestation. Agricultural Land greatly increases its surface by agricultural expansion. Increased surface Shrub and herbaceous vegetation, linked to natural regeneration of the potential analysis area. The Anthropogenic areas have considerable growth linked to urban sprawl. With these results the creation of a strategy Incentives, starting from a baseline allows the construction of a Policy Payment for Environmental Services in the country and for the benefit of citizens is proposed. These future strategies projected greater conservation area while maintaining the connectivity of ecosystems, biodiversity and adequate sustainable production.El presente trabajo analiza la influencia del Programa Socio Bosque en la dinámica de los Servicios Ambientales de los Bosques Secos Deciduos del Ecuador. Estos bosques son formaciones situadas en la planicie cálida de la costa ecuatoriana, poseen la característica de perder el 75% de sus hojas durante la época seca. Actualmente se registra una superficie de 467.210,89 hectáreas de Bosque Seco Deciduo, distribuidas a lo largo de las provincias de Manabí, Guayas, Santa Elena, El Oro y Loja. Desde el 2008, el Ministerio del Ambiente del Ecuador, implementa una política de incentivos para la conservación de bosques nativos, los participantes o socios de este programa se comprometen a la conservación de las áreas, a cambio reciben un incentivo económico por cada hectárea conservada. Dentro del estudio se identificó un área potencial de análisis que corresponde a 372.492,77 hectáreas, estos espacios fueron comparados mediante un estudio multitemporal en tres períodos (1990-2000), (2001-2008) y (2009.2012), identificando los cambios de cobertura vegetal y uso del suelo en el área de influencia de los bosques secos deciduos. Los resultados del estudio multitemporal muestran un cambio de las siguientes clases: los Bosques Nativos poseen una tendencia de disminución de superficie básicamente por efectos de la deforestación. Las Tierras Agropecuarias aumentan considerablemente su superficie por la expansión agrícola. Se identificó un aumento de superficie de Vegetación Arbustiva y Herbácea, vinculado a la regeneración natural del área potencial de análisis. Las Zonas Antrópicas tienen un crecimiento considerable ligado a la gran expansión urbana. Con estos resultados se propone la creación de una Estrategia de Incentivos, que partiendo de una línea base permita la construcción de una Política de Pago por Servicios Ambientales en el país y en beneficio de la ciudadanía. Estas futuras estrategias proyectan mayor área de conservación manteniendo la conectividad de ecosistemas, la biodiversidad y una adecuada producción sostenible