RESUMEN
Lead (Pb) is a developmental neurotoxicant. We have demonstrated that perinatally Pb-exposed rats consume more ethanol than their control counterparts, a response that seems to be mediated by catalase (CAT) and centrally-formed acetaldehyde, ethanol's first metabolite with attributed reinforcing effects in the brain. The present study sought to disrupt ethanol intake (2-10% ethanol v/v) in rats exposed to 220 ppm Pb or filtered water during gestation and lactation. Thus, to block brain CAT expression, a lentiviral vector coding for a shRNA against CAT (LV-antiCAT vector) was microinfused in the posterior ventral tegmental area (pVTA) either at the onset or towards the end of a chronic voluntary ethanol consumption test. At the end of the study, rats were euthanized and pVTA dissected to measure CAT expression by Western blot. The LV-antiCAT vector administration not only reversed, but also prevented the emergence of the elevated ethanol intake reported in the perinatally Pb-exposed animals, changes that were supported by a significant reduction in CAT expression in the pVTA. These results provide further evidence of the crucial role of this enzyme in the reinforcing properties of ethanol and in the impact of the perinatal Pb programming to challenging events later in life.
Asunto(s)
Consumo de Bebidas Alcohólicas/prevención & control , Encéfalo/enzimología , Catalasa/biosíntesis , Etanol/toxicidad , Plomo/toxicidad , Efectos Tardíos de la Exposición Prenatal/enzimología , Consumo de Bebidas Alcohólicas/efectos adversos , Animales , Encéfalo/efectos de los fármacos , Catalasa/antagonistas & inhibidores , Catalasa/genética , Etanol/administración & dosificación , Femenino , Regulación Enzimológica de la Expresión Génica , Plomo/administración & dosificación , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/prevención & control , Ratas , Ratas WistarRESUMEN
Gestational diabetes mellitus (GDM) has increased in recent years. Although the cellular and molecular mechanisms involved in GDM-increased risk factors to offspring remained poorly understood, some studies suggested an association between an increase in oxidative stress induced by maternal hyperglycemia and complications for both mothers and newborns. Here, we investigated the impact of maternal hyperglycemia followed by maternal insulin replacement during lactation on the expression of antioxidant enzymes and mast cell number in offspring ventral prostate (VP) at puberty. Pregnant rats were divided into three groups: control (CT); streptozotocin-induced maternal hyperglycemia (MH); and MH plus maternal insulin replacement during lactation (MHI). Male offspring were euthanized at postnatal day (PND) 60 and the VP was removed and processed for histology and Western blotting analyses. Maternal hyperglycemia delayed prostate maturation, and increased mast cell number catalase (CAT), superoxide dismutase (SOD), glutatione-s-transferase (GST-pi), and cyclooxygenase-2 (Cox-2) expression in the offspring of hyperglycemic dams. Maternal insulin replacement restored VP structure, mast cell number and antioxidant protein expression, except for Cox-2, which remained higher in the MHI group. Thus, an increase in oxidative stress induced by intrauterine hyperglycemia impacts prostate development and maturation, which persists until puberty. The overall improvement of maternal metabolism after insulin administration contributes to the restoration of prostate antioxidant enzymes and secretory function. Taken together, our results highlighted that imbalanced physiological maternal-fetal interaction contributes to the impairment of reproductive performance of the offspring from diabetic mothers. Anat Rec, 300:291-299, 2017. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Diabetes Gestacional/metabolismo , Mastocitos/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Próstata/metabolismo , Animales , Glucemia/metabolismo , Recuento de Células , Ciclooxigenasa 2/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/patología , Diabetes Gestacional/tratamiento farmacológico , Diabetes Gestacional/enzimología , Diabetes Gestacional/patología , Femenino , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Insulina/farmacología , Insulina/uso terapéutico , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/patología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/enzimología , Efectos Tardíos de la Exposición Prenatal/patología , Próstata/efectos de los fármacos , Próstata/enzimología , Próstata/patología , Ratas , Ratas WistarRESUMEN
Conduct problems in childhood and adolescence are significant precursors of crime and violence in young adulthood. The purpose of the current study is to test the interaction between prenatal maternal smoking and COMT Val(158)Met in conduct problems and crime in the 1993 Pelotas Birth Cohort Study. Conduct problems were assessed through the parent version of the Strengths and Difficulties Questionnaire at ages 11 and 15 years. A translated version of a confidential self-report questionnaire was used to collect criminal data at 18 years of age. Negative binomial regression analyses showed an association between prenatal maternal smoking and SDQ conduct problem scores (IRR = 1.24; 95% CI: 1.14-1.34; p < 0.001) at 11 years of age. However, no evidence was found for an association between COMT genotypes and conduct scores or for an interaction between maternal smoking and this gene in predicting conduct problems. Very similar results were obtained using the 15 years conduct scores and crime measure at age 18. Prenatal maternal smoking was associated with crime (IRR = 1.28; 95% CI: 1.09-1.48; p = 0.002) but neither COMT genotypes nor the possible interaction between gene and maternal smoking were significantly associated with crime. Replications of GxE findings across different social contexts are critical for testing the robustness of findings.
Asunto(s)
Catecol O-Metiltransferasa/genética , Crimen , Efectos Tardíos de la Exposición Prenatal/enzimología , Efectos Tardíos de la Exposición Prenatal/genética , Problema de Conducta , Fumar/efectos adversos , Adolescente , Brasil , Estudios de Cohortes , Demografía , Femenino , Humanos , Masculino , EmbarazoRESUMEN
This study presents a comprehensive view of the histological and functional status of the prostate of adult rat offspring of mothers subjected to gestational diabetes induced by alloxan. The ventral prostate of male adult offspring of diabetic (DP) or normal (CP) mothers was evaluated for collagen fibres, cell death, fibroblasts, smooth muscle cells, cell proliferation, matrix metalloproteinases (MMPs), androgen receptors (AR), transforming growth factor ß1 (TGFß-1), catalase and total antioxidant activity. The prostates of DP animals were lower in weight than those of the CP group. The DP group also exhibited hyperglycaemia and hypotestosteronemia, higher cell proliferation and AR expression, a reduction in α-actin (possibly interfering with the reproductive function of the prostate), and enhanced activity of MMP-2, although the absolute content of MMP-2 was lower in this group. These findings were associated with increased TGFß-1 and decreased collagen distribution. The prostates of DP rats additionally exhibited reductions in catalase and total antioxidant activity. Thus, rats developing in a diabetic intrauterine environment have glycaemic and hormonal changes that impact on the structure and physiology of the prostate in adulthood. The increased AR expression possibly leads to elevated cell proliferation. Stromal remodelling was characterized by enhanced activity of MMP-2 and collagen degradation, even with increased TGFß-1 activation. These changes associated with increased oxidative stress might interfere with tissue architecture and glandular homeostasis.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Gestacional , Metaloproteinasa 2 de la Matriz/biosíntesis , Embarazo en Diabéticas , Efectos Tardíos de la Exposición Prenatal/enzimología , Próstata/enzimología , Animales , Colágeno/metabolismo , Femenino , Regulación de la Expresión Génica , Hiperglucemia/enzimología , Hiperglucemia/etiología , Hiperglucemia/patología , Masculino , Estrés Oxidativo , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Próstata/patología , Ratas , Ratas Wistar , Receptores Androgénicos/biosíntesis , Factor de Crecimiento Transformador beta1/biosíntesisRESUMEN
Prenatal cigarette smoke exposure (PCSE) has been associated with physiological and developmental changes that may be related to an increased risk for childhood and adult neuropsychiatric diseases. The present study investigated locomotor activity and cholinesterase enzyme activity in rats, following PCSE and/or ketamine treatment in adulthood. Pregnant female Wistar rats were exposed to 12 commercially filtered cigarettes per day for a period of 28 days. We evaluated motor activity and cholinesterase activity in the brain and serum of adult male offspring that were administered acute subanesthetic doses of ketamine (5, 15 and 25 mg/kg), which serves as an animal model of schizophrenia. To determine locomotor activity, we used the open field test. Cholinesterase activity was assessed by hydrolysis monitored spectrophotometrically. Our results show that both PCSE and ketamine treatment in the adult offspring induced increase of locomotor activity. Additionally, it was observed increase of acetylcholinesterase and butyrylcholinesterase activity in the brain and serum, respectively. We demonstrated that animals exposed to cigarettes in the prenatal period had increased the risk for psychotic symptoms in adulthood. This also occurs in a dose-dependent manner. These changes provoke molecular events that are not completely understood and may result in abnormal behavioral responses found in neuropsychiatric disorders, such as schizophrenia.
Asunto(s)
Colinesterasas/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Esquizofrenia/fisiopatología , Humo/efectos adversos , Productos de Tabaco/efectos adversos , Animales , Modelos Animales de Enfermedad , Femenino , Ketamina/administración & dosificación , Ketamina/farmacología , Exposición Materna/efectos adversos , Actividad Motora/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/enzimología , Ratas , Ratas Wistar , Esquizofrenia/inducido químicamente , Esquizofrenia/enzimología , Factores de TiempoRESUMEN
In the present study, we evaluated the effects of the ethanolic extract (EE) of Cipura paludosa on locomotor, and anxiety- and depression-like behaviors of adult rats exposed to MeHg during early development. Additionally, the antioxidant enzymes catalase (CAT) and selenium-glutathione peroxidase (Se-GPx) were measured in cortical, hippocampal, and cerebellar tissues. Pregnant Wistar rats were treated by gavage with a single dose of MeHg (8 mg/kg) on gestational day 15, the developmental stage critical for cortical neuron proliferation. Moreover, prenatal MeHg exposure inhibited CAT and Se-GPx in the cortex and cerebellum. Chronic treatment with the EE of C. paludosa attenuated these emotional and antioxidant deficits induced by prenatal MeHg toxic exposure. This study provides novel evidence that developmental exposure to MeHg can affect not only cognitive functions but also locomotor, and anxiety- and depression-like behaviors.
Asunto(s)
Conducta Animal/efectos de los fármacos , Iridaceae/química , Compuestos de Metilmercurio/toxicidad , Organogénesis/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Efectos Tardíos de la Exposición Prenatal/prevención & control , Contaminantes Químicos del Agua/toxicidad , Animales , Catalasa/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Masculino , Exposición Materna/efectos adversos , Aprendizaje por Laberinto/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/enzimología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratas , Ratas Wistar , NataciónRESUMEN
We had previously shown that prenatal exposure to Zn-deficient diets induces an increase in blood pressure and impairs renal function in adult rats. The aim of the present study was to investigate if moderate Zn restriction during early growth periods, fetal life and lactation would induce impairment in the vascular and renal NO system and alterations in plasma lipid profile. We also investigated if these effects persisted into adult life, even when a Zn-replete diet was provided after weaning. Pregnant rats were fed control (30 parts per million (ppm)) or low (8 ppm) Zn diets throughout gestation up to weaning. Afterwards, male offspring from low-Zn mothers were assigned to low- or control-Zn diets during 60 d. Male offspring from control mothers were fed a control diet. Animals exposed to Zn restriction showed low birth weight, increased systolic blood pressure and serum TAG levels, and decreased glomerular filtration rate in adulthood. Zn restriction induced a decrease in vascular and renal NO synthase activity and a reduced expression of the endothelial NO synthase isoform in aorta. A control-Zn diet during post-weaning growth returned TAG levels to normal but was unsuccessful in normalising systolic blood pressure, glomerular filtration rate or NO system activity in Zn-deficient offspring. Zn restriction during fetal life, lactation and/or post-weaning growth induced alterations in the vascular and renal NO system and in lipid metabolism that could contribute to the programming of hypertension and renal dysfunction in adulthood.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Endotelio Vascular/metabolismo , Óxido Nítrico Sintasa/metabolismo , Efectos Tardíos de la Exposición Prenatal , Fenómenos Fisiologicos de la Nutrición Prenatal , Zinc/deficiencia , Animales , Animales Recién Nacidos , Peso al Nacer , Dieta , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Crecimiento , Lactancia , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/enzimología , Isoformas de Proteínas , Ratas , Ratas Wistar , Triglicéridos/sangre , Destete , Zinc/farmacologíaRESUMEN
The paraoxonase 1 (PON1) enzyme prevents low-density lipoprotein oxidation and also detoxifies the oxon derivatives of certain neurotoxic organophosphate (OP) pesticides. PON1 activity in infants is low compared to adults, rendering them with lower metabolic and antioxidant capacities. We made a longitudinal comparison of the role of genetic variability on control of PON1 phenotypes in Mexican-American mothers and their children at the time of delivery (n=388 and 338, respectively) and again 7 years later (n=280 and 281, respectively) using generalized estimating equations models. At age 7, children's mean PON1 activities were still lower than those of mothers. This difference was larger in children with genotypes associated with low PON1 activities (PON1(-108TT), PON1(192QQ), and PON1(-909CC)). In mothers, PON1 activities were elevated at delivery and during pregnancy compared to 7 years later when they were not pregnant (p<0.001). In non-pregnant mothers, PON1 polymorphisms and haplotypes accounted for almost 2-fold more variation of arylesterase (AREase) and chlorpyrifos-oxonase (CPOase) activity than in mothers at delivery. In both mothers and children, the five PON1 polymorphisms (192, 55, -108, -909, -162) explained a noticeably larger proportion of variance of paraoxonase activity (62-78%) than AREase activity (12.3-26.6%). Genetic control of PON1 enzymatic activity varies in children compared to adults and is also affected by pregnancy status. In addition to known PON1 polymorphisms, unidentified environmental, genetic, or epigenetic factors may also influence variability of PON1 expression and therefore susceptibility to OPs and oxidative stress.
Asunto(s)
Arildialquilfosfatasa/genética , Arildialquilfosfatasa/metabolismo , Haplotipos/genética , Americanos Mexicanos/genética , Efectos Tardíos de la Exposición Prenatal/enzimología , Efectos Tardíos de la Exposición Prenatal/genética , Adulto , Arildialquilfosfatasa/antagonistas & inhibidores , Arildialquilfosfatasa/biosíntesis , Niño , Estudios de Cohortes , Activación Enzimática/genética , Femenino , Genotipo , Humanos , Recién Nacido , Estudios Longitudinales , Masculino , Organofosfatos/administración & dosificación , Polimorfismo Genético/genética , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Factores de Tiempo , Adulto JovenRESUMEN
Low birth weight has been associated with increased obesity in adulthood. It has been shown that dietary salt restriction during intrauterine life induces low birth weight and insulin resistance in adult Wistar rats. The present study had a two-fold objective: to evaluate the effects that low salt intake during pregnancy and lactation has on the amount and distribution of adipose tissue; and to determine whether the phenotypic changes in fat mass in this model are associated with alterations in the activity of the renin-angiotensin system. Maternal salt restriction was found to reduce birth weight in male and female offspring. In adulthood, the female offspring of dams fed the low-salt diet presented higher adiposity indices than those seen in the offspring of dams fed a normal-salt diet. This was attributed to the fact that adipose tissue mass (retroperitoneal but not gonadal, mesenteric or inguinal) was greater in those rats than in the offspring of dams fed a normal diet. The adult offspring of dams fed the low-salt diet, compared to those dams fed a normal-salt diet, presented the following: plasma leptin levels higher in males and lower in females; plasma renin activity higher in males but not in females; and no differences in body weight, mean arterial blood pressure or serum angiotensin-converting enzyme activity. Therefore, low salt intake during pregnancy might lead to the programming of obesity in adult female offspring.
Asunto(s)
Adiposidad/fisiología , Dieta Hiposódica/efectos adversos , Efectos Tardíos de la Exposición Prenatal/etiología , Tejido Adiposo/crecimiento & desarrollo , Animales , Presión Sanguínea/fisiología , Femenino , Leptina/sangre , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/enzimología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratas , Ratas Wistar , Renina/sangre , Renina/metabolismo , Sistema Renina-Angiotensina/fisiología , Factores Sexuales , Cloruro de Sodio Dietético/administración & dosificaciónRESUMEN
Transcriptional factors and signalling molecules from intracellular metabolism modulate a complex set of events during brain development. Neurotransmitter and neuromodulator synthesis and their receptor expressions vary according to different stages of brain development. The dynamics of signalling systems is often accompanied by alterations in enzyme expression and activity. Adenosine is a neuromodulator that controls the release of several neurotransmitters, including acetylcholine, which is an important neurotransmitter during brain development. Caffeine is a non-specific antagonist of adenosine receptors and can reach the immature brain. We evaluated the effects of rat maternal caffeine intake (1g/L) on acetylcholine degradation and acetylcholinesterase expression from hippocampus of 7-, 14- and 21-day-old neonates in caffeine-treated and control groups. Caffeine was not able to change the age-dependent increase of acetylcholinesterase activity or the age-dependent decrease of acetylcholinesterase expression. However, caffeine promoted an increase of acetylcholinesterase activity (42%) without modifications on the level of acetylcholinesterase mRNA transcripts in 21-day-old rats. Considering the high score of phosphorylatable residues on acetylcholinesterase, this profile can be associated with a possible regulation by specific phosphorylation sites. These results highlight the ability of maternal caffeine intake to interfere on cholinergic neurotransmission during brain development.