0000000001331316

AUTHOR

Raúl Ballestín

Endocytosis in cultured neurons is altered by chronic alcohol exposure.

Endocytosis is required for many cellular pivotal processes, including membrane recycling, nutrient uptake, and signal transduction. This complex process is particularly relevant in polarized cells, such as neurons. Previous studies have demonstrated that alcohol alters intracellular traffic, including endocytosis, in several cell types. However, information on the effect of chronic alcohol exposure on this process in neurons is scarce. As an approach, we investigated the effect of alcohol exposure on the internalization of two widely used endocytic markers, albumin and transferrin, in developing hippocampal neurons in primary culture. The effect of this treatment on the levels of several r…

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Chronic ethanol exposure alters the levels, assembly, and cellular organization of the actin cytoskeleton and microtubules in hippocampal neurons in primary culture.

The organization and dynamics of microtubules (MTs) and the actin cytoskeleton are critical for the correct development and functions of neurons, including intracellular traffic and signaling. In vitro ethanol exposure impairs endocytosis, exocytosis, and nucleocytoplasmic traffic in astrocytes and alters endocytosis in cultured neurons. In astrocytes, these effects relate to changes in the organization and/or function of MTs and the actin cytoskeleton. To evaluate this possibility in hippocampal cultured neurons, we analyzed if chronic ethanol exposure affects the levels, assembly, and cellular organization of both cytoskeleton elements and the possible underlying mechanisms of these effec…

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El uso de las redes sociales en la docencia universitaria: estudio piloto con Instagram

Instagram es una red social atractiva y versátil muy utilizada por jóvenes y adolescentes. Además de ser una herramienta interesante para contactar con otros o llenar el tiempo libre, puede tener una gran utilidad en el proceso de enseñanza-aprendizaje, ya que los alumnos dedican mucho tiempo a su uso y les resulta muy atractiva. En el presente trabajo se muestra un estudio piloto basado en un proyecto de innovación educativa desarrollado con el objetivo de fomentar el uso de Instagram como recurso educativo en la docencia universitaria de asignaturas de Psicobiología. Se propuso a los estudiantes que buscaran avances científicos recientes relacionados con el área de Psicobiología y Neuroci…

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Protein traffic is an intracellular target in alcohol toxicity

Eukaryotic cells comprise a set of organelles, surrounded by membranes with a unique composition, which is maintained by a complex synthesis and transport system. Cells also synthesize the proteins destined for secretion. Together, these processes are known as the secretory pathway or exocytosis. In addition, many molecules can be internalized by cells through a process called endocytosis. Chronic and acute alcohol (ethanol) exposure alters the secretion of different essential products, such as hormones, neurotransmitters and others in a variety of cells, including central nervous system cells. This effect could be due to a range of mechanisms, including alcohol-induced alterations in the d…

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Astrocytes of the murine model for Down Syndrome Ts65Dn display reduced intracellular ionic zinc.

Zinc is an essential trace element that is critical for a large number of structural proteins, enzymatic processes and transcription factors. In the brain, zinc ions are involved in synaptic transmission. The homeostasis of zinc is crucial for cell survival and function, and cells have developed a wide variety of systems to control zinc concentration. Alterations in free zinc concentration have been related with brain dysfunction. Down Syndrome individuals present alterations in free zinc concentration and in some of the proteins related with zinc homeostasis. We have analyzed the amount of free zinc and the zinc chelating protein metallothionein 3 in the astrocytes using primary cultures o…

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Ethanol reduces zincosome formation in cultured astrocytes.

Aims Zinc is an ion that participates in basic cellular and tissular functions. Zinc deficiency is present in many physiological and health problems affecting most body organs, including the brain. Among the circumstances involved in zinc deficiency, ethanol consumption is probably one of the most frequent. A dietary zinc supplement has been proposed as possibly being an efficient method to palliate zinc deficiency. Astrocytes form part of the hematoencephalic barrier, and they are apparently implicated in the homeostasis of the neuronal medium. In this work, we analyze the effect of ethanol on extracellular zinc management by rat astrocytes in culture. Methods Intracellular levels of 'free…

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Correction: Indomethacin blocks the increased conditioned rewarding effects of cocaine induced by repeated social defeat

It is well established that repeated social defeat stress can induce negative long-term consequences such as increased anxiety-like behavior and enhances the reinforcing effect of psychostimulants in rodents. In the current study, we evaluated how the immune system may play a role in these long-term effects of stress. A total of 148 OF1 mice were divided into different experimental groups according to stress condition (exploration or social defeat) and pre-treatment (saline, 5 or 10 mg/kg of the anti-inflammatory indomethacin) before each social defeat or exploration episode. Three weeks after the last social defeat, anxiety was evaluated using an elevated plus maze paradigm. After this tes…

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Voluntary wheel running protects against the increase in ethanol consumption induced by social stress in mice

Abstract Previous studies have shown that exposure to social defeat (SD), a model of social stress, produces a long-term increase in the consumption of ethanol, most likely through an increase in the neuroinflammation response. The aim of the present study was to evaluate whether exposure to physical activity in the form of voluntary wheel running (VWR) could block the increase in ethanol consumption and the neuroinflammatory response induced by social stress. Mice were exposed to either 4 sessions of repeated social defeat (RSD) or a non-stressful experience. During the whole procedure, half of the mice were exposed to controlled physical activity, being allowed 1 h access to a low-profile…

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Social defeat-induced increase in the conditioned rewarding effects of cocaine: Role of CX3CL1

Abstract Social stress is associated with higher vulnerability to drug use, as it enhances the reinforcing effects of psychostimulants in rodents. Furthermore, continued or severe stress induces a proinflammatory state of microglial activation and augmented cytokine production. The aim of the present work was to evaluate the role of fractalkine [C-X3-C motif ligand 1 (CX3CL1)], an inflammatory chemokine, in the increased conditioned rewarding effects of cocaine in animals exposed to social defeat stress. In addition, we measured the signaling cascade pathway of CX3CL1 in the hippocampus (HPC) (including p-ERK/ERK, p-p38/p38 MAPK, p-p65/p65 NFκB and p-CREB/CREB ratios). The glutamate recepto…

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Polyphosphoinositide Metabolism and Golgi Complex Morphology in Hippocampal Neurons in Primary Culture is Altered by Chronic Ethanol Exposure

Aims : Ethanol affects not only the cytoskeletal organization and activity, but also intracellular trafficking in neurons in the primary culture. Polyphosphoinositide (PPIn) are essential regulators of many important cell functions, including those mentioned, cytoskeleton integrity and intracellular vesicle trafficking. Since information about the effect of chronic ethanol exposure on PPIn metabolism in neurons is scarce, this study analysed the effect of this treatment on three of these phospholipids. Methods : Phosphatidylinositol (PtdIns) levels as well as the activity and/or levels of enzymes involved in their metabolism were analysed in neurons chronically exposed to ethanol. The level…

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Neuroinflammatory and behavioral susceptibility profile of mice exposed to social stress towards cocaine effects.

Using the social defeat (SD) model, numerous studies have shown that stressed mice display an enhanced response to the motivational effects of cocaine in the self-administration (SA) and conditioned-place preference (CPP) paradigms. However, not all subjects exposed to stress express its harmful effects. Some are particularly susceptible to the deleterious effects of repeated SD, while resilient mice successfully cope with stressful experiences and display adjusted psychological functioning after stress. Vulnerability to develop stress-related disorders, such as depression, has been linked to coping strategies and more recently to individual differences in the immune system. However, no stu…

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Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine rewa

The kynurenine (KYN) pathway of tryptophan (TRP) degradation is activated by stress and inflammatory factors. It is now well established that social stress induces the activation of the immune system, with central inflammation and KYN metabolism being two of the main factors linking stress with depression. The aim of the present study was to evaluate the long-lasting changes in the KYN pathway induced by social defeat (SD) associated with the resilience or susceptibility to an increase in the conditioned rewarding effects of cocaine. Mice were exposed to repeated SD and 3 weeks later, a conditioned place preference (CPP) induced by a subthreshold dose of cocaine (1.5 mg/kg) was developed. K…

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Indomethacin blocks the increased conditioned rewarding effects of cocaine induced by repeated social defeat

It is well established that repeated social defeat stress can induce negative long-term consequences such as increased anxiety-like behavior and enhances the reinforcing effect of psychostimulants in rodents. In the current study, we evaluated how the immune system may play a role in these long-term effects of stress. A total of 148 OF1 mice were divided into different experimental groups according to stress condition (exploration or social defeat) and pre-treatment (saline, 5 or 10 mg/kg of the anti-inflammatory indomethacin) before each social defeat or exploration episode. Three weeks after the last social defeat, anxiety was evaluated using an elevated plus maze paradigm. After this tes…

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Astrocitos y zinc: alteraciones inducidas en modelos in vitro de los síndromes alcohólico fetal y de Down

El zinc es un elemento traza esencial; crítico para un gran número de proteínas estructurales, procesos enzimáticos y factores de transcripción. Esta variada ubicación en las biomoléculas hace que participe en multitud de funciones celulares y tisulares. En el caso particular del cerebro, los iones zinc están implicados, además, en la transmisión sináptica. Por todo ello, la homeostasis del zinc es crucial para la función y supervivencia de las células, y estas han desarrollado una amplia variedad de sistemas para el control de la concentración de zinc en las células. La deficiencia de zinc puede acabar desencadenando muchos problemas fisiológicos y de salud, que afectan a la mayoría de los…

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Social defeat stress: mechanisms underlying the increase in rewarding effects of drugs of abuse

Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to social defeat experiences (brief episodes of social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how social defeat stress induces longlasting consequence…

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Oxytocin prevents the increase of cocaine-related responses produced by social defeat

The neuropeptide oxytocin (OXT) plays a critical role in the regulation of social and emotional behaviors. OXT plays a role in stress response and in drug reward, but to date no studies have evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated social defeat (RSD). During the social defeat procedure, 1 mg/kg of OXT was administered 30 min before each episode of RSD. Three weeks after the last defeat, the effects of cocaine on the conditioned place preference (CPP), locomotor sensitization and the self-administration (SA) paradigms were evaluated. The influence of OXT on the levels of BDNF in the prefrontal cortex (PFC), striatum an…

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Oxytocin prevents the increase of cocaine-related responses produced by social defeat

The neuropeptide oxytocin (OXT) plays a critical role in the regulation of social and emotional behaviors. OXT plays a role in the stress response and in drug reward, but to date no studies have evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated social defeat (SD). During the social defeat procedure, 1 mg/kg of OXT was administered 30 minutes before each episode of SD. Three weeks after the last defeat, the effects of cocaine on conditioned place preference (CPP), locomotor sensitization and the self-administration (SA) paradigm were evaluated. Our results confirm that raising the levels of OXT during social defeat stress can bl…

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