Neonatal treatment with para-chlorophenylalanine (pCPA) induces adolescent hyperactivity associated with changes in the paraventricular nucleus Crh and Trh expressions.

Disruption of the brain serotoninergic (5-HT) system during development induces long-lasting changes in molecular profile, cytoarchitecture, and function of neurons, impacting behavioral regulation throughout life. In male and female rats, we investigate the effect of neonatal tryptophan hydroxylase (TPH) inhibition by using para-chlorophenylalanine (pCPA) on the expression of 5-HTergic system components and neuropeptides related to adolescent social play behavior regulation. We observed sex-dependent 5-HT levels decrease after pCPA-treatment in the dorsal raphe nucleus (DRN) at 17 and 35 days. Neonatal pCPA-treatment increased playing, social and locomotory behaviors assessed in adolescent rats of both sexes. The pCPA-treated rats demonstrated decreased Crh (17 days) and increased Trh (35 days) expression in the hypothalamic paraventricular nucleus (PVN). There was sex dimorphism in Htr2c (17 days) and VGF (35 days) in the prefrontal cortex, with the females expressing higher levels of it than males. Our results indicate that neonatal pCPA-treatment results in a long-lasting and sex-dependent DRN 5-HT synthesis changes, decreased Crh, and increased Trh expression in the PVN, resulting in a hyperactivity-like phenotype during adolescence. The present work demonstrates that the impairment of TPH function leads to neurobehavioral disorders related to hyperactivity and impulsivity, such as attention deficit hyperactivity disorder (ADHD).

Water deprivation induces hypoactivity in rats independently of oxytocin receptor signaling at the central amygdala.

Introduction: Vasopressin (AVP) and oxytocin (OXT) are neuropeptides produced by magnocellular neurons (MCNs) of the hypothalamus and secreted through neurohypophysis to defend mammals against dehydration. It was recently demonstrated that MCNs also project to limbic structures, modulating several behavioral responses. Methods and Results: We found that 24 h of water deprivation (WD) or salt loading (SL) did not change exploration or anxiety-like behaviors in the elevated plus maze (EPM) test. However, rats deprived of water for 48 h showed reduced exploration of open field and the closed arms of EPM, indicating hypoactivity during night time. We evaluated mRNA expression of glutamate decarboxylase 1 (Gad1), vesicular glutamate transporter 2 (Slc17a6), AVP (Avpr1a) and OXT (Oxtr) receptors in the lateral habenula (LHb), basolateral (BLA) and central (CeA) amygdala after 48 h of WD or SL. WD, but not SL, increased Oxtr mRNA expression in the CeA. Bilateral pharmacological inhibition of OXTR function in the CeA with the OXTR antagonist L-371,257 was performed to evaluate its possible role in regulating the EPM exploration or water intake induced by WD. The blockade of OXTR in the CeA did not reverse the hypoactivity response in the EPM, nor did it change water intake induced in 48-h water-deprived rats. Discussion: We found that WD modulates exploratory activity in rats, but this response is not mediated by oxytocin receptor signaling to the CeA, despite the upregulated Oxtr mRNA expression in that structure after WD for 48 h.

Moderate ethanol exposure during early ontogeny of the rat alters respiratory plasticity, ultrasonic distress vocalizations, increases brain catalase activity, and acetaldehyde-mediated ethanol intake.

Early ontogeny of the rat (late gestation and postnatal first week) is a sensitive period to ethanol's positive reinforcing effects and its detrimental effects on respiratory plasticity. Recent studies show that acetaldehyde, the first ethanol metabolite, plays a key role in the modulation of ethanol motivational effects. Ethanol brain metabolization into acetaldehyde via the catalase system appears critical in modulating ethanol positive reinforcing consequences. Catalase system activity peak levels occur early in the ontogeny. Yet, the role of ethanol-derived acetaldehyde during the late gestational period on respiration response, ultrasonic vocalizations (USVs), and ethanol intake during the first week of the rat remains poorly explored. In the present study, pregnant rats were given a subcutaneous injection of an acetaldehyde-sequestering agent (D-penicillamine, 50 mg/kg) or saline (0.9% NaCl), 30 min prior to an intragastric administration of ethanol (2.0 g/kg) or water (vehicle) on gestational days 17-20. Respiration rates (breaths/min) and apneic episodes in a whole-body plethysmograph were registered on postnatal days (PDs) 2 and 4, while simultaneously pups received milk or ethanol infusions for 40-min in an artificial lactation test. Each intake test was followed by a 5-min long USVs emission record. On PD 8, immediately after pups completed a 15-min ethanol intake test, brain samples were collected and kept frozen for catalase activity determination. Results indicated that a moderate experience with ethanol during the late gestational period disrupted breathing plasticity, increased ethanol intake, as well brain catalase activity. Animals postnatally exposed to ethanol increased their ethanol intake and exerted differential affective reactions on USVs and apneic episodes depending on whether the experience with ethanol occur prenatal or postnatally. Under the present experimental conditions, we failed to observe, a clear role of acetaldehyde mediating ethanol's effects on respiratory plasticity or affective states, nevertheless gestational acetaldehyde was of crucial importance in determining subsequent ethanol intake affinity. As a whole, results emphasize the importance of considering the participation of acetaldehyde in fetal programming processes derived from a brief moderate ethanol experience early in development, which in turn, argues against "safe or harmless" ethanol levels of exposure.

Ethanol's disruptive effects upon early breathing plasticity and blood parameters associated with hypoxia and hypercapnia.

Early ethanol exposure affects respiratory neuroplasticity; a risk factor associated with the Sudden Infant Death Syndrome. High and chronic ethanol doses exert long-lasting effects upon respiratory rates, apneic episodes and ventilatory processes triggered by hypoxia. The present study was performed in 3-9-day-old rat pups. Respiratory processes under normoxic and hypoxic conditions were analyzed in pups intoxicated with different ethanol doses which were pre-exposed or not to the drug. A second major goal was to examine if acute and/or chronic early ethanol exposure affects blood parameters related with hypercapnic or hypoxic states. In Experiment 1, at postnatal day 9, animals previously treated with ethanol (2.0 g/kg) or vehicle (0.0 g/kg) were tested sober or intoxicated with 0.75, 1.37 or 2.00 g/kg ethanol. The test involved sequential air conditions defined as initial normoxia, hypoxia and recovery normoxia. Motor activity was also evaluated. In Experiment 2, blood parameters indicative of possible hypoxic and hypercapnic states were assessed as a function of early chronic or acute experiences with the drug. The main results of Experiment 1 were as follows: i) ethanol's depressant effects upon respiratory rates increased as a function of sequential treatment with the drug (sensitization); ii) ethanol inhibited apneic episodes even when employing the lowest dose at test (0.75 g/kg); iii) the hyperventilatory response caused by hypoxia negatively correlated with the ethanol dose administered at test; iv) ventilatory long-term facilitation (LTF) during recovery normoxia was observed in pups pre-exposed to the drug and in pups that received the different ethanol doses at test; v) self-grooming increased in pups treated with either 1.37 or 2.00 g/kg ethanol. The main result of Experiment 2 indicated that acute as well as chronic ethanol exposure results in acidosis-hypercapnia. The results indicate that early and brief experiences with ethanol are sufficient to affect different respiratory plasticity processes as well as blood biomarkers indicative of acidosis-hypercapnia. An association between the LTF process and the acidosis-hypercapnic state caused by ethanol seems to exist. The mentioned experiences with the drug are sufficient to result in an anomalous programming of respiratory patterns and metabolic conditions.

Neonatal Serotonin Depletion Induces Hyperactivity and Anxiolytic-like Sex-Dependent Effects in Adult Rats.

The serotoninergic system plays an important role in the ontogeny of the mammalian central nervous system, and changes in serotonin production during development may lead to permanent changes in brain cytoarchitecture and function. The present study investigated the programming effects of neonatal serotonin depletion on behavior and molecular components of the serotoninergic system in adult male and female rats. Subcutaneous para-chlorophenylalanine (pCPA) administration (100 mg kg-1) was performed daily on postnatal days 8-16 to deplete brain serotonin content. During adulthood, elevated plus-maze, open field, social interaction, forced swimming, and food, saline, and sucrose intake tests were performed. Relative expression of serotonin neurotransmission components in several brain areas was determined by qPCR. Additionally, serotonin immunofluorescence and neuropeptide mRNA expression were assessed in dorsal raphe (DRN) and paraventricular (PVN) nuclei, respectively. Rat performance in behavioral tests demonstrated a general increase in locomotor activity and active escape behavior as well as decreased anxiety-like behavior after neonatal brain serotonin depletion. The behavioral programming effects due to neonatal serotonin depletion were more pronounced in females than males. At the gene expression level, the mRNA of Tph1 and Tph2 were lower in DRN while Htr2c was higher in the amygdala of pCPA-treated males, while Htr1a, Htr2c, Oxt, Avp, Crh, and Trh were not different in any treatments or sex in PVN. The results indicate that neonatal serotonin depletion has long-term consequences on locomotion and anxiety-like behavior associated with long-lasting molecular changes in the brain serotoninergic system in adult rats.

Learning experiences comprising central ethanol exposure in rat neonates: Impact upon respiratory plasticity and the activity of brain catalase.

Fetal ethanol exposure represents a risk factor for sudden infant death syndrome, and the respiratory effects of fetal ethanol exposure promote hypoxic ischemic consequences. This study analyzes central ethanol's effects upon breathing plasticity during an ontogenetic stage equivalent to the human third gestational trimester. Ethanol's unconditioned breathing effects and their intervention in learning processes were examined. Since central ethanol is primarily metabolized via the catalase system, we also examined the effects of early history with the drug upon this system. During postnatal days 3, 5, and 7 (PDs 3-7), pups were intracisternally administered with vehicle or ethanol (300 mg%). They were tested in a plethysmograph scented or not scented with ethanol odor. The state of intoxication attenuated the onset of apneas, a phenomenon that is suggestive of ethanol's anxiolytic effects given the state of arousal caused by the novel environment and the stress of ethanol administration. At PD9, pups were evaluated when sober under sequential air conditions (initial-normoxia, hypoxia, and recovery-normoxia), with or without the presence of ethanol odor. Initial apneic episodes increased when ethanol intoxication was previously associated with the odor. Pups then ingested ethanol, and brain catalase activity was determined. Pre-exposure to ethanol intoxication paired with the odor of the drug resulted in heightened enzymatic activity. Central ethanol exposure appears to exert antianxiety effects that attenuate apneic disruptions. However, during withdrawal, the cues associated with such effects elicit an opposite reaction. The activity of the catalase system was also dependent upon learning processes that involved the association of environmental stimuli and ethanol intoxication.

Maternal separation induces long-term changes in mineralocorticoid receptor in rats subjected to chronic stress and treated with tianeptine.

PURPOSE: The aim of this study was to analyze whether early maternal separation would result in long-term, persistent alterations in stress response in adulthood, altering mineralocorticoid receptor immunoreactivity (MR-ir) in the dorsal hippocampal areas [CA1, CA2, CA3 and dentate gyrus (DG)], paraventricular nucleus of the hypothalamus and medial and central nucleus of the amygdala, key structures involved in stress response regulation. We also analyzed whether chronic treatment with the antidepressant tianeptine reverses these possible changes. MATERIAL AND METHODS: Male Wistar rats were subjected to daily maternal separation for 4.5 h during 3 weeks or left undisturbed. As adults, they were exposed to chronic stress during 24 days or left undisturbed, and they were also daily treated with tianeptine (10 mg/kg i.p.) or isotonic solution. RESULTS: In the CA2 and DG areas of the dorsal hippocampus, there was an increase in MR-ir in non-maternally separated and chronic stressed groups. Tianeptine raised MR-ir in the CA3. In the DG, control and maternally separated + chronic stress groups treated with tianeptine showed more MR-ir than their respective vehicle groups. In the paraventricular nucleus, tianeptine decreased MR-ir in non-separated groups, but not in maternally separated rats. CONCLUSIONS: Our results support findings that early-life events induce long-term changes in stress response regulation, persistent into adulthood, which are manifested during challenges in later life, and that treatment with tianeptine, which tends to attenuate the hypothalamus-pituitary-adrenal axis dysregulation, depends on the individual experience of each rat.

Exploring the role of the DSM-5 performance-only specifier in adolescents with social anxiety disorder.

The DSM-5 social anxiety disorder section has recently added the performance-only specifier for individuals whose anxiety is limited to speaking or performing in public. The impact of the DSM-5 performance-only specifier remains a neglected area. The sample comprised 44 healthy controls and 50 adolescents with a clinical diagnosis of SAD (20% met criteria for the performance-only specifier). Findings revealed that adolescents with the specifier had a later age of onset; lower levels of depression, social anxiety symptomatology and clinical severity; and a lesser degree of comorbidity relative to adolescents with SAD but excluding the performance-only specifier. Specifiers only evidenced higher (cognitive) social anxiety symptomatology compared to healthy controls. Results of this study also suggested that the performance-only specifier may correspond to a mild form of social anxiety disorder. Data also revealed that SAD exists on a continuum of severity among healthy controls, specifier participants, and those with both interactional and performance fears, which is consistent with a dimensional structure for SAD. Finally, findings suggested a unique comorbid pattern for specifiers and those adolescents with SAD but excluding the performance-only specifier. The implications of these findings for the etiology, assessment, classification, and treatment of social anxiety in youth are discussed.

How does early maternal separation and chronic stress in adult rats affect the immunoreactivity of serotonergic neurons within the dorsal raphe nucleus?

Vulnerability to emotional disorders like depression derives from interactions between early and late environments, including stressful conditions. The serotonin (5HT) system is strongly affected by stress and chronic unpredictable stress can alter the 5HT system. We evaluated the distribution of active serotonergic neurons in the dorsal raphe nucleus (DR) through immunohistochemistry in maternally separated and chronically stressed rats treated with an antidepressant, tianeptine, whose mechanism of action is still under review. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50-74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle. We found an interaction between the effects of MS and chronic unpredictable stress on Fos-5HT immunoreactive cells at mid-caudal level of the DR. MS-chronically stressed rats showed an increase of Fos-5HT immunoreactive cells compared with AFR-chronically stressed rats. The ventrolateral (DRL/VLPAG) and dorsal (DRD) subdivisions of the DR were significantly more active than the ventral part (DRV). At the rostral level of the DR, tianeptine decreased the number of Fos-5HT cells in DR in the AFR groups, both unstressed and stressed. Overall, our results support the idea of a match in phenotype exhibited when the early and the adult environment correspond.

Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

Surface creasing instability of soft polyacrylamide cell culture substrates.

Efforts to understand and engineer cell behavior in mechanically soft environments frequently employ two-dimensional cell culture substrates consisting of thin hydrogel layers with low elastic modulus supported on rigid substrates to facilitate culturing, imaging, and analysis. Here we characterize how an elastic creasing instability of the gel surface may occur for the most widely used soft cell culture substrate, polyacrylamide hydrogels, and show that stem cells respond to and change their behavior due to these surface features. The regions of stability and corresponding achievable ranges of modulus are elucidated in terms of the monomer and cross-linker concentrations, providing guidance for the synthesis of both smooth and creased soft cell substrates for basic and applied cell engineering efforts.

Tianeptine influence on plasmatic catecholamine levels and anxiety index in rats under variable chronic stress after early maternal separation.

The aim of this work was to determine the effect of chronic treatment with 5 mg/kg of tianeptine in male adult Wistar rats separated from the mother as neonates and submitted to variable chronic stress, plasma catecholamines, and anxiety. The plus maze test was performed in order to calculate the anxiety index and catecholamine levels were determined by high-pressure liquid chromatography. Both stress and maternal separation elevated catecholamine levels without affecting anxiety. In the maternally separated stress group, tianeptine decreased epinephrine. Anxiety was reduced in the maternally separated unstressed tianeptine group. Also, all groups showed a tendency to lower anxiety index.

Creasing instability of surface-attached hydrogels.

The unidirectional expansion of a thin surface-attached polymer gel upon swelling by solvent generates a biaxial compressive stress within the gel. For sufficiently large stresses, a mechanical instability can occur in which the free surface locally buckles and folds against itself to form creases. This instability has important implications for the design of biomaterials, smart surfaces, and sensors, since it places a fundamental limit on the amount of swelling that a surface-attached polymer layer may undergo without forming topographical features. However, while this instability was first observed more than a century ago, the amount of compression necessary to form creases has never been systematically studied. Using a model system of poly(acrylamide-co-sodium acrylate) hydrogels, we establish that the onset of creasing corresponds to an effective linear compressive strain of ∼ 0.33, or a change in thickness by a factor of ∼ 2. Remarkably, this value varies only slightly with modulus over a range of ∼ 0.6-24 kPa and is independent of gel thickness from 3 µm-1 mm, in excellent agreement with theoretical predictions. This instability is reversible, with creases disappearing as the degree of swelling is lowered, but surfaces exhibit a significant memory for crease locations when subsequently re-swelled.

Evaluación a la organización del Departamento de Enfermería de un Hospital Gíneco-Obstétrico de V nivel de atención Hospital Gíneco-Obstétrico Isidro Ayora / Evaluation to the organization of the Department of Infirmary of a Hospital Gi'neco-Obste'trico of V attention level Hospital Gi'neco-Obste'trico Isidro Ayora

Para realizar la presente investigación se ha basado en la auscultación directa de los problemas latentes en la Organización del departamento de Enfermería de una Unidad Operativa que corresponde al V Nivel de Atención de salud, ya que el Departamento de Enfermería es el núcleo vital de la Institución, lo que contribuye a brindar una atención de calidad al usuario que acude a esta Unidad Operativa. Esta investigación sobre "Evaluación de la Organización del Departamento de Enfermería del Hospital Gíneco-Obstétrico Isidro Ayora", realizado durante el transcurso del Internado Rotativo en esta Institución se establece la importancia de la Evaluación de la Organización del Departamento, utilizando el método científico y basándonos en entrevistas y encuestas al personal para obtener datos verídicos y la comprobación del Tipo de Organización que mantiene actualmente. Se analizó la situación de Salud de nuestro país, especialmente la de Hospitales Estatales y de la población Materno Infantil. En la situación de Salud se analizó desde la década del 60 hasta la actualidad en donde el país ha sufrido cambios económicos, políticos y culturales repercutiendo también en la salud; en cuanto a salud Materno Infantil que es la población olvidada durante muchos años, en la actualidad existen reformas en beneficio del binomio madre-niño, ampliando la cobertura de atención, disminuyendo a la vez las tasas de mortalidad de éste binomio para el cumplimiento de éste objetivo, dependiendo de presupuesto que el estado asigne a los profesionales del sector salud, especialmente de Enfermeras quienes están las 24 horas del día junto al paciente. Para el éxito del trabajo en equipo, es necesario que éste Departamento tenga una Organización efectiva que garantice la atención integral. La organización proporciona el marco formal dentro del cual se verifica el proceso administrativo, sistema de trabajo, de comunicaciones e identidad para los individuos es decir fomentar la satisfacción en el cumplimiento de sus labores. Se debe anotar además que el Departamento de Enfermería de toda Institución Hospitalaria, debe funcionar de acuerdo a un Manual Técnico Administrativo...