Postnatal administration of allopregnanolone modifies glutamate release but Not BDNF content in striatum samples of rats prenatally exposed to ethanol

Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABA A receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c.) administered to juvenile male rats (day 21 of age) on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8). Prenatal ethanol administration decreased the K+-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABA A receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.Fil: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas; ArgentinaFil: Estrella, Cecilia R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: García Menéndez, Sebastián Marcelo Manuel. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Lara, Hernán E.. Universidad de Chile; ChileFil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor β1 (TGF-β1) in hippocampus: effect of a TGF-β1 oligo-antisense

BACKGROUND: Corticosterone reduction produced by adrenalectomy (ADX) induces apoptosis in dentate gyrus (DG) of the hippocampus, an effect related to an increase in the expression of the pro-apoptotic gene bax. However it has been reported that there is also an increase of the anti-apoptotic gene bcl-2, suggesting the promotion of a neuroprotective phenomenon, perhaps related to the expression of transforming growth factor β1 (TGF-β1). Thus, we have investigated whether TGF-β1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-β1 with an antisense oligonucleotide (ASO) administered intracerebrally in corticosterone depleted rats. RESULTS: It was observed an increase of apoptosis in DG, 2 and 5 days after ADX, in agreement with a reduction of corticosterone levels. However, the effect of ADX on the number of apoptotic positive cells in DG was decreased 5 days after the lesion. In CA1–CA3 regions, the effect was only observed 2 days after ADX. TGF-β1 mRNA levels were increased 2 days after ADX. The sustained intracerebro-ventricular administration of a TGF-β1 ASO via an osmotic mini pump increased apoptosis levels in CA and DG regions 5 days after ADX as well as sham-operated control animals. No significant effect was observed following a scrambled-oligodeoxynucleotide treatment. CONCLUSION: The changes in both the pattern and the magnitude of apoptotic-cell morphology observed 2 and 5 days after ADX suggest that, as a consequence of the reduction of corticosteroids, some trophic mechanisms restricting cell death to a particular time window are elicited. Sustained intracerebral administration of TGF-β1 ASO increased the apoptosis promoted by ADX, suggesting that TGF-β1 plays an anti-apoptotic role in vivo in hippocampus

Genomic erosion in the assessment of species extinction risk and recovery potential

Many species are facing unprecedented population size declines and deterioration of their environment. This exposes species to genomic erosion, which we define here as the damage inflicted to a species’ genome or gene pool due to a loss of genetic diversity, an increase in expressed genetic load, maladaptation, and/or genetic introgression. The International Union for Conservation of Nature (IUCN) bases its extinction risk assessments on direct threats to population size and habitat. However, it does not assess the long-term impacts of genomic erosion, and hence, it is likely to underestimate the extinction risk of many species. High-quality whole genome sequence data that is currently being generated could help improve extinction risk assessments. Genomic data contains information about a species’ past demography, its genome-wide genetic diversity, the incidence of genetic introgression, as well as the genetic load of deleterious mutations. Computer modelling of these data enables forecasting of population trajectories under different management scenarios. In this Perspective, we discuss the threats posed by genomic erosion. Using evolutionary genomic simulations, we argue that whole genome sequence data provides critical information for assessing the extinction risk and recovery potential of species. Genomics-informed assessments of the extinction risk complement the IUCN Red List, and such genomics-informed conservation is invaluable in guiding species recovery programs in the UN’s Decade on Ecosystem Restoration and beyond

Comorbidities in Chilean patients with psoriasis: a Global Healthcare Study on Psoriasis

Background: Psoriasis is a chronic inflammatory skin disease associated with several important medical comorbidities. There are scant data available on the comorbidities of patients with psoriasis in South America. Aim: To examine the comorbidity profile of adult patients with psoriasis in Chile and its association with severity of psoriasis. Methods: This was a multicentre, cross-sectional study involving 16 hospitals and clinics in Chile, which used a 48-item questionnaire to study clinician- and patient-reported outcomes and comorbidities. Inferential analyses were performed by psoriasis severity, using Fisher exact test, Student t-test and multivariable logistic regression. Results: In total, 598 adult patients with psoriasis were included (51.1% male; mean age 49.2 ± 15.1 years); 48.5% mild and 51.4% moderate to severe; Psoriasis Area and Severity Index 11.6 ± 11.5; body surface area 14.7 ± 18.2%. Plaque psoriasis was the most common phenotype (90.2%), followed by guttate (13.4%). Psoriatic arthritis occurred in 27.3% of patients. Comorbidities were reported in 60.2% of all patients with psoriasis. Frequent concomitant diseases were obesity (25.3%), hypertension (24.3%), Type 2 diabetes mellitus (T2DM) (18.7%), dyslipidaemia (17.4%), metabolic syndrome (16.7%) and depression (14.4%). After adjustment, significant associations were found between moderate to severe psoriasis and obesity, T2DM and nonalcoholic fatty liver disease (NAFLD) compared with mild psoriasis. Conclusions: We report a large study of comorbidities, including depression, dyslipidaemia, T2DM and NAFLD, in people with psoriasis in Chile. The prevalence of comorbidities with psoriasis in Chile appears similar to that found in Western countries, and emphasizes the importance of assessing patients with psoriasis for risk factors for and presence of, comorbid disease in a multidisciplinary setting

Real-time genomics for One Health

The ongoing degradation of natural systems and other environmental changes has put our society at a crossroad with respect to our future relationship with our planet. While the concept of One Health describes how human health is inextricably linked with environmental health, many of these complex interdependencies are still not well-understood. Here, we describe how the advent of real-time genomic analyses can benefit One Health and how it can enable timely, in-depth ecosystem health assessments. We introduce nanopore sequencing as the only disruptive technology that currently allows for real-time genomic analyses and that is already being used worldwide to improve the accessibility and versatility of genomic sequencing. We showcase real-time genomic studies on zoonotic disease, food security, environmental microbiome, emerging pathogens, and their antimicrobial resistances, and on environmental health itself – from genomic resource creation for wildlife conservation to the monitoring of biodiversity, invasive species, and wildlife trafficking. We stress why equitable access to real-time genomics in the context of One Health will be paramount and discuss related practical, legal, and ethical limitations

Guanethidine-mediated destruction of ovarian sympathetic nerves disrupts ovarian development and function in rats

Immunosympathectomy produced by treatment of newborn rats with antibodies to nerve growth factor (NGF) delays ovarian development and disrupts estrous cyclicity. While these alterations have been ascribed to loss of sympathetic neurons innervating the ovary, the treatment also causes partial loss of ovarian sensory innervation. The present experiments were undertaken to determine if selective interference with ovarian noradrenergic/sympathetic action would result in alterations of ovarian development similar to those caused by NGF antibodies (NGF Ab). We have used two approaches to disrupt catecholamine action on ovarian cells: 1) inhibition of /3-adrenoreceptors by local delivery of receptor blockers to the ovaries of juvenile rats; and 2) elimination of the sympathetic innervation by long term postnatal treatment with guanethidine (GD), an adrenergic neuron blocking agent. When GD is administered chronically it produces an autoimmune-mediated destruction of peripheral sympathetic ne

Role of RFRP-3 in the development of cold stress-induced polycystic ovary phenotype in rats

2018 Society for Endocrinology RFamide-related peptide (RFRP-3) is a regulator of GnRH secretion from the brain, but it can also act in human ovary to influence steroidogenesis. We aimed to study the putative local role of RFRP-3 in the ovary and its potential participation in the development of a polycystic ovary phenotype induced by chronic sympathetic stress (cold stress). We used adult Sprague–Dawley rats divided into control and stressed groups. In both groups, we studied the effect of intraovarian exposure to RFRP-3 on follicular development and plasma ovarian steroid concentrations. We also tested the effect of RFRP-3 on ovarian steroid production in vitro. Chronic in vivo intraovarian exposure to RFRP-3 decreased basal testosterone concentrations and cold stress-induced progesterone production by the ovary. In vitro, RFRP-3 decreased hCG-induced ovarian progesterone and testosterone secretion. Immunohistochemistry and mRNA expression analysis showed a decrease in Rfrp and expr

Immature rat ovaries become revascularized rapidly after autotransplantation and show a gonadotropin-dependent increase in angiogenic factor gene expression

When the ovaries of 23-day-old juvenile rats are transplanted to an ectopic site, they recover within 1 week the ability to control gonadotropin secretion via steroid negative feedback. Vascular corrosion casting followed by scanning electron microscopy revealed that the transplanted ovary becomes profusely revascularized within 48 h after transplantation. Vascular ingrowth was accompanied by a 40- to 60-fold increase in expression of the genes encoding two angiogenic factors, vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGFβ1), as assessed by RNA blot hybridization of the corresponding mRNAs. Although TGFβ3 mRNA levels also increased, no changes in the levels of mRNAs encoding other putative angiogenic factors, such as TGFα, basic fibroblast growth factor, and TGFβ2, were observed. Hybridization histochemistry demonstrated that in intact ovaries, VEGF mRNA is mainly expressed in granulosa cells of the cumulus oophorus and thecal cells of large antral f

Hormonal programming across the lifespan

Hormones influence countless biological processes across an animal's lifespan. Many hormone-mediated events occur within developmental sensitive periods, during which hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous selective critical periods in development with different targets being affected during different periods. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal steroid hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of critical hormone receptor genes across dev