Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats

Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect

Interaction between neonatal maternal deprivation and serum leptin levels on metabolism, pubertal development, and sexual behavior in male and female rats

Background: Maternal deprivation (MD) during neonatal life can have long-term effects on metabolism and behavior, with males and females responding differently. We previously reported that MD during 24 h at postnatal day (PND) 9 blocks the physiological neonatal leptin surge in both sexes. It is known that modifications in neonatal leptin levels can affect metabolism in adulthood. Thus, we hypothesized that at least some of the long-term metabolic changes that occur in response to MD are due to the decline in serum leptin during this critical period of development. Hence, we predicted that treatment with leptin during MD would normalize these metabolic changes, with this response also differing between the sexes. Methods: MD was carried-out in Wistar rats for 24 h on PND9. Control and MD rats of both sexes were treated from PND 9 to 13 with leptin (3 mg/kg/day sc) or vehicle. Weight gain, food intake, glucose tolerance, and pubertal onset were monitored. Sexual behavior was analyzed in males. Rats were killed at PND90, and serum hormones and hypothalamic neuropeptides involved in metabolic control and reproduction were measured. Results were analyzed by three-way analysis of covariance using sex, MD, and leptin treatment as factors and litter as the covariate and employing repeated measures where appropriate. Results: In males, MD advanced the external signs of puberty and increased serum insulin and triglyceride levels and hypothalamic proopiomelanocortin mRNA levels at PND90. Neonatal leptin treatment normalized these effects. In contrast, MD decreased circulating triglycerides, as well as estradiol levels, in females at PND90 and these changes were also normalized by neonatal leptin treatment. Neonatal leptin treatment also had long-term effects in control rats as it advanced the external signs of puberty in control males, but delayed them in females. Neonatal leptin treatment increased serum insulin and hypothalamic mRNA levels of the leptin receptor and cocaine- and amphetamine-regulated transcript in control males and increased orexin mRNA levels in controls of both sexes. Although pubertal onset in males was advanced by either MD or neonatal leptin treatment in males and delayed by leptin treatment in females, the mRNA levels of hypothalamic neuropeptides and receptors related to reproduction were not affected by MD or neonatal leptin treatment in either sex at PND90. Conclusions: These findings indicate that some of the long-term changes in metabolic and reproductive parameters induced by MD, such as advanced pubertal onset and increased hypothalamic proopiomelanocortin (POMC) expression, hyperinsulinemia, and hypertriglyceridemia in adult males and decreased serum triglyceride and estradiol levels in females, are most likely due to the decrease in leptin levels during the period of MD

Accurate determination of key surface properties that determine the efficient separation of bovine milk BSA and LF proteins

The aim of this work is to accurately measure fundamental surface properties, i.e., zeta potential, isoelectric point and protein size that determine the optimal separation conditions of Bovine serum albumin and lactoferrin, two high added value food proteins whose similarity in weight makes their separation a scientific and technical challenge. The systematic study of these proteins’ surface properties was performed under different conditions: (i) 3.0 < pH < 10.0, (ii) electrolyte type: KCl, NaCl and CaCl2 and concentration (0.01–0.1 M KCl) and (iii) protein concentration in the range of 0.04–4.0 g L-1 for BSA and 0.01–1.0 g L-1 for LF with the objective of establishing the optimal separation conditions. Finally, the comparison of the experimental and theoretically calculated values revealed significant deviations under specific conditions, highlighting the simplicity of the theoretical assumptions and leading to the conclusion that the use of experimental surface properties is still needed for the correct design of food protein separation processes.Financial support from the Projects CTQ2011-25262, CTM2011- 23912 and CTQ2012- 31639 (Ministerio de Economía y Competitividad-MINECO/SPAIN and Fondo Europeo de Desarrollo Regional-FEDER) is gratefully acknowledged

The Relationship between Depressive Symptoms, Quality of Life and miRNAs 8 Years after Bariatric Surgery

Altres ajuts: Universidad de Málaga, UMA20-FEDERJA-144; Junta de Andalucia, PI-0194-2017, C-0028-2018, RC-005-2020, DOC_00288 and DOC_01095Background: There are conflicting results on whether weight loss after bariatric surgery (BS) might be associated with quality of life (QoL)/depressive symptomatology. We aim to determine whether BS outcomes are associated with QoL/depressive symptomatology in studied patients at the 8-year follow-up after BS, as well as their relationship with different serum proteins and miRNAs. Methods: A total of 53 patients with class III obesity who underwent BS, and then classified into "good responders" and "non-responders" depending on the percentage of excess weight lost (%EWL) 8 years after BS (%EWL ≥ 50% and %EWL < 50%, respectively), were included. Basal serum miRNAs and different proteins were analysed, and patients completed tests to evaluate QoL/depressive symptomatology at 8 years after BS. Results: The good responders group showed higher scores on SF-36 scales of physical functioning, role functioning-physical, role functioning-emotional, body pain and global general health compared with the non-responders. The expression of hsa-miR-101-3p, hsa-miR-15a-5p, hsa-miR-29c-3p, hsa-miR-144-3p and hsa-miR-19b-3p were lower in non-responders. Hsa-miR-19b-3p was the variable associated with the response to BS in a logistic regression model. Conclusions: The mental health of patients after BS is limited by the success of the intervention. In addition, the expression of basal serum miRNAs related to depression/anxiety could predict the success of BS

Reworlding: participatory design capabilities to tackle socio-environmental challenges

Rising societal polarisations around health and climate crises have brought more attention to the close relations between social and environmental challenges. These polarisations triggered an interest in the participatory design (PD) field in developing approaches that enhance connections between diverse actors operating across societal and environmental sectors. However, the capabilities needed for these approaches have not been sufficiently articulated in PD research and education. To fill in this gap, we define 'reworlding' as an operation of self-critique within PD that engages with capabilities needed to reveal and articulate radical interdependencies between humans and more-than-humans, across social and environmental worlds, and within situated contexts. We propose both the redefinition of the design capabilities needed for (re)connecting these worlds (retracing, reconnecting, reimagining and reinstitutioning), as well as a reconsideration of learning environments where these capabilities can be tested and enhanced

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Modelos experimentales para el estudio de las acciones hipotalámicas y extra-hipotalámicas de la leptina neonatal

En los últimos años, nuestro grupo de investigación ha caracterizado un modelo de estrés neonatal, concretamente un modelo de separación materna (SM) en ratas Wistar durante 24h en el día postnatal (DPN) 9. En el estudio de efectos a corto, medio y largo plazo de la SM, hemos encontrado modificaciones psiconeuroinmunoendocrinas que se manifiestan tanto en la adolescencia como en la edad adulta y en muchos casos de manera sexo-dimórfica. En concreto, hemos mostrado como dicho modelo de estrés neonatal induce diversas alteraciones comportamentales que afectan a la memoria y respuestas emocionales que iban acompañadas de alteraciones a nivel cerebral, tanto en hipocampo como en corteza frontal. Además, los animales SM muestran alteraciones a nivel metabólico y endocrino tales como una afectación en la ganancia de peso que se extiende hasta bien entrada la edad adolescente y modificaciones en diversas hormonas como la leptina, la testosterona y la adiponectina. No sólo encontramos alteraciones cerebrales en adolescencia y edad adulta, sino ya a los 13 días de edad, en regiones tanto hipotalámicas como extra-hipotalámicas. Uno de los hallazgos que más nos llamó la atención fue que los niveles de leptina se hayan drásticamente reducidos durante el período de separación materna, DPN 9-10, una reducción aún observable a DPN13. Recientemente se ha descrito la existencia de un periodo crítico (DPN5 a DPN10) en roedores, durante el cual se da una elevación fisiológica de leptina, con un pico a DPN9, que tiene una función neurotrófica sobre el hipotálamo en desarrollo..

La filiera risicola

Studio riguardante le prospettive economiche e occupazionali della filiera risicola in Itali

Modulatory influences of estradiol and other anorexigenic hormones on metabotropic, Gi/o-coupled receptor function in the hypothalamic control of energy homeostasis

The appetite suppressant actions of estradiol are due to its ability to attenuate orexigenic signals and potentiate anorexigenic signals. The work from my laboratory has shown that male guinea pigs are more sensitive to the hyperphagic and hypothermic effects of cannabinoids than their female counterparts. Cannabinoid sensitivity is further dampened by the activational effects of estradiol. This occurs via the hypothalamic feeding circuitry, where estradiol rapidly attenuates the cannabinoid CB1 receptor-mediated presynaptic inhibition of glutamatergic input onto anorexigenic proopiomelanocortin (POMC) neurons in the arcuate nucleus. This disruption is blocked by the estrogen receptor antagonist ICI 182,780, and associated with increased expression of phosphatidylinositol-3-kinase (PI3K). Moreover, the ability of estradiol to reduce both the cannabinoid-induced hyperphagia and glutamate release onto POMC neurons is abrogated by the PI3K inhibitor PI 828. The peptide orphanin FQ/nociceptin (OFQ/N) activates opioid receptor-like (ORL)1 receptors to hyperpolarize and inhibit POMC neurons via the activation of postsynaptic G protein-gated, inwardly-rectifying (GIRK) channels. We have demonstrated that the fasting-induced hyperphagia observed in ORL1-null mice is blunted compared to wild type controls. In addition, the ORL1 receptor-mediated activation of GIRK channels in POMC neurons from ovariectomized female rats is markedly impaired by estradiol. The estrogenic attenuation of presynaptic CB1 and postsynaptic ORL1 receptor function may be part of a more generalized mechanism through which anorexigenic hormones suppress orexigenic signaling. Indeed, we have found that leptin robustly suppresses the OFQ/N-induced activation of GIRK channels in POMC neurons. Furthermore, its ability to augment excitatory input onto POMC neurons is blocked by PI 828. Thus, estradiol and other hormones like leptin reduce energy intake at least partly by activating PI3K to disrupt the pleiotropic functions of Gi/o-coupled receptors that inhibit anorexigenic POMC neurons.PHSCooperative Research Thematic Networks in HealthInstituto de Salud Carlos III (España)Western University of Health SciencesDepto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEpu