Persona: Carrillo Urbano, Beatriz
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Carrillo Urbano
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Publicación Relationship between autism spectrum disorder and pesticides: A systematic review of human and preclinical models(MDPI, 2021-05-03) Biosca Brull, Judit; Pérez Fernández, Cristian; Mora, Santiago; Carrillo Urbano, Beatriz; Pinos Sánchez, María Elena; Maria Conejo, Nelida; Collado Guirao, Paloma; Arias, Jorge L.; Martín Sánchez, Fernando; Sánchez Santed, Fernando; Colomina, Maria TeresaAutism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.Publicación Physiological and brain alterations produced by high-fat diet in male and female rats can be modulated by increased levels of estradiol during critical periods of development(Taylor and Francis Online, 2017-07-11) Carrillo Urbano, Beatriz; Collado Guirao, Paloma; Díaz, Francisca; Chowen, Julie A.; Pérez Izquierdo, María Ángeles; Pinos Sánchez, María ElenaBackground: Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. Objective: Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. Methods: Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA. Results: Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development. Discussion: HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.Publicación G protein-coupled estrogen receptor immunoreactivity in the rat hypothalamus is widely distributed in neurons, astrocytes and oligodendrocytes, fluctuates during the estrous cycle and is sexually dimorphic(Karger International, 2021-06-29) Marraudino, Marilena; Carrillo Urbano, Beatriz; Bonaldo, Brigitta; Llorente, Ricardo; Campioli, Elia; Garate, Iciar; Pinos Sánchez, María Elena; Garcia Segura, Luis; Collado Guirao, Paloma; Grassi, DanielaIntroduction: The membrane-associated G protein-coupled estrogen receptor 1 (GPER) mediates the regulation by estradiol of arginine-vasopressin immunoreactivity in the supraoptic and paraventricular hypothalamic nuclei of female rats and is involved in the estrogenic control of hypothalamic regulated functions, such as food intake, sexual receptivity, and lordosis behavior. Objective: To assess GPER distribution in the rat hypothalamus. Methods: GPER immunoreactivity was assessed in different anatomical subdivisions of five selected hypothalamic regions of young adult male and cycling female rats: the arcuate nucleus, the lateral hypothalamus, the paraventricular nucleus, the supraoptic nucleus, and the ventromedial hypothalamic nucleus. GPER immunoreactivity was colocalized with NeuN as a marker of mature neurons, GFAP as a marker of astrocytes, and CC1 as a marker of mature oligodendrocytes. Results: GPER immunoreactivity was detected in hypothalamic neurons, astrocytes, and oligodendrocytes. Sex and regional differences and changes during the estrous cycle were detected in the total number of GPER-immunoreactive cells and in the proportion of neurons, astrocytes, and oligodendrocytes that were GPER-immunoreactive. Conclusions: These findings suggest that estrogenic regulation of hypothalamic function through GPER may be different in males and females and may fluctuate during the estrous cycle in females.Publicación Relationship between prenatal or postnatal exposure to pesticides and obesity: a systematic review(MDPI, 2021-07-04) Pinos Sánchez, María Elena; Carrillo Urbano, Beatriz; Merchán, Ana; Biosca Brull, Judit; Pérez Fernández, Cristian; Colomina, María Teresa; Sánchez Santed, Fernando; Martín Sánchez, Fernando; Collado Guirao, Paloma; Arias, Jorge L.; Conejo, Nélida M.In recent years, the worldwide prevalence of overweight and obesity among adults and children has dramatically increased. The conventional model regarding the onset of obesity is based on an imbalance between energy intake and expenditure. However, other possible environmental factors involved, such as the exposure to chemicals like pesticides, cannot be discarded. These compounds could act as endocrine-disrupting chemicals (EDC) that may interfere with hormone activity related to several mechanisms involved in body weight control. The main objective of this study was to systematically review the data provided in the scientific literature for a possible association between prenatal and postnatal exposure to pesticides and obesity in offspring. A total of 25 human and 9 animal studies were analyzed. The prenatal, perinatal, and postnatal exposure to organophosphate, organochlorine, pyrethroid, neonicotinoid, and carbamate, as well as a combined pesticide exposure was reviewed. This systematic review reveals that the effects of pesticide exposure on body weight are mostly inconclusive, finding conflicting results in both humans and experimental animals. The outcomes reviewed are dependent on many factors, including dosage and route of administration, species, sex, and treatment duration. More research is needed to effectively evaluate the impact of the combined effects of different pesticides on human health.Publicación Influence of early maternal separation on susceptibility to the activity-based anorexia model in male and female Sprague Dawley rats(Elsevier, 2022-11) Kojo Morgan, Godstime Stephen; Mata, Yolanda; Carrillo Urbano, Beatriz; Pellón Suárez de Puga, Ricardo; Collado Guirao, Paloma; Gotti, Stefano; Pinos Sánchez, María ElenaA principal animal paradigm employed in Anorexia Nervosa (AN) study is the activity-based anorexia (ABA) model. The model's efficacy in recapitulating the core features of AN in humans allows for the study of the parameters involved in the disorder. The current study examined the susceptibility to the ABA protocol in the presence of a significant stressor (maternal separation) in male and female Sprague Dawley rats. More importantly, we analysed the sex-differences on activity levels during different periods of the ABA protocol to determine the period(s) influencing the most pathological weight loss. Both components of the ABA protocol contributed to the subjects’ bodyweight loss. Stress in the first two weeks of development conferred a protective effect in males. Time spent and activity levels on the running wheel were higher in females compared to males. Hyperactivity in ABA subjects was observed during the food-anticipatory activity (FAA) and postprandial activity in males and during the FAA and nocturnal activity periods in females. This study aids in understanding the effect of intensity of activity during specific periods on the pathological weight loss in ABA rats. These observations are informative for therapies aimed at ameliorating body mass index in AN patients.Publicación Blocking of Estradiol Receptors ERα, ERβ and GPER During Development, Differentially Alters Energy Metabolism in Male and Female Rats(Elsevier, 2020) Díaz González, Francisca; Chowen, Julie A.; Grassi, Daniela; Pinos Sánchez, María Elena; Carrillo Urbano, Beatriz; Collado Guirao, PalomaEstradiol not only participates in the regulation of energy metabolism in adulthood, but also during the first stages of life as it modulates the alterations induced by under- and over-nutrition. The objectives of the present study were to determine: 1) If estradiol is involved in the normal programming of energy metabolism in rats; 2) If there is a specific window of time for this programming and 3) If males and females are differentially vulnerable to the action of this hormone. Estrogen receptors (ER) α, ERβ and GPER were blocked by their specific antagonists MPP, PHTPP and G15, respectively, from postnatal day (P) 1 (the day of birth) to P5 or from P5 to P13. Physiological parameters such as body weight, fat depots and caloric intake were then analysed at P90. Hypothalamic AgRP, POMC, MC4R, ERα, ERβ and GPER mRNA levels and plasma levels of estradiol, were also studied. We found that blocking ER receptors from P5 to P13 significantly decreases long-term body weight in males and hypothalamic POMC mRNA levels in females. The blocking of ERs from P1 to P5 only affected plasma estradiol levels in females. The present results indicate programming actions of estradiol from P5 to P13 on body weight in male and POMC expression in female rats and emphasize the importance of including both sexes in metabolic studies. It is necessary to unravel the mechanisms that underlie the actions of estradiol on food intake, both during development and in adulthood, and to determine how this programming differentially takes place in males and females.