Thyroid hormones and retinoids: a possible link between genes and environment in schizophrenia

Prova tipográfica (In Press)Phenotypic discordance for schizophrenia in monozygotic twins clearly indicates involvement of environmental factors as key determinants in disease development. Positive findings from genome scans, linkage and association studies apply in only a minority of those affected, while post-mortem brain investigations reveal altered expression of genes and proteins involved in numerous neurodevelopmental, metabolic and neurotransmitter pathways. Such altered expressions could result, on the one hand, from mutations in coding regions or polymorphisms in the promoter and regulatory regions in genes within those areas identified by gene searches or, on the other hand, from inadequate amounts of modulators, transporters and synthesizers of transcription factors necessary for regulation of the putative genes. Hormones and vitamins are such modulators. They could serve as bridges between genes and environment in schizophrenia. Multiple evidence supports the suggestion of retinoids and thyroid hormones as plausible actors in these roles. Both are not only essential for normal development of the central nervous system but also regulate the expression of many neurotransmitters, their synthesizing enzymes and receptors, and other genes in broader signaling transduction cascades affecting pathways that are altered in response to treatment. Functional and positional candidate genes include retinoic acid and thyroid hormone receptors, retinaldehyde dehydrogenases and deiodinases, which synthesize the powerful morphogens, retinoic acid and triiodothyronine, and the enzymes involved in their inactivation. This review highlights selective evidence supporting the retinoid and thyroid hormone hypotheses of schizophrenia

Construyendo una facultad de medicina innovadora en Portugal : la experiencia de la Universidad de Minho

Hallelujah!’, proclaimed in October 8, 2001, 27 years after the first proposal delivered to the Portuguese government, the project’s founder, Professor Joaquim Pinto Machado, at the beginning of educational activities at the School of Medicine (formerly School of Health Sciences), University of Minho (SM-UMinho), Braga, Portugal. This manuscript reviews the strategy implemented and the outcomes 15 years after welcoming the first medical students.‘¡Aleluya!’. Así, 27 años después de la primera propuesta presentada al gobierno portugués, el fundador del proyecto, el Profesor Joaquim Pinto Machado, proclamaba el 8 de octubre de 2001 el inicio de las actividades educativas de la nueva Facultad de Medicina (anteriormente Escuela de Ciencias de la Salud) de la Universidad de Minho (SM-UMinho), Braga, Portugal. Este artículo revisa la estrategia utilizada para la implementación de la nueva facultad y los resultados 15 años después de dar la bienvenida a los primeros estudiantes de medicinainfo:eu-repo/semantics/publishedVersio

Hormone-Mediated Gene Regulation and Bioinformatics: Learning One from the Other

The ability to manage the constantly growing clinically relevant information in genetics available on the internet is becoming crucial in medical practice. Therefore, training students in teaching environments that develop bioinformatics skills is a particular challenge to medical schools. We present here an instructional approach that potentiates learning of hormone/vitamin mechanisms of action in gene regulation with the acquisition and practice of bioinformatics skills. The activity is integrated within the study of the Endocrine System module. Given a nucleotide sequence of a hormone or vitamin-response element, students use internet databases and tools to find the gene to which it belongs. Subsequently, students search how the corresponding hormone/vitamin influences the expression of that particular gene and how a dysfunctional interaction might cause disease. This activity was presented for four consecutive years to cohorts of 50–60 students/year enrolled in the 2nd year of the medical degree. 90% of the students developed a better understanding of the usefulness of bioinformatics and 98% intend to use web-based resources in the future. Since hormones and vitamins regulate genes of all body organ systems, this activity successfully integrates the whole body physiology of the medical curriculum

Blood-brain-barriers in aging and in Alzheimer's disease

The aging process correlates with a progressive failure in the normal cellular and organ functioning; these alterations are aggravated in Alzheimer's disease (AD). In both aging and AD there is a general decrease in the capacity of the body to eliminate toxic compounds and, simultaneously, to supply the brain with relevant growth and nutritional factors. The barriers of the brain are targets of this age related dysfunction; both the endothelial cells of the blood--brain barrier and the choroid plexus epithelial cells of the blood-cerebrospinal fluid barrier decrease their secretory capacity towards the brain and their ability to remove toxic compounds from the brain. Additionally, during normal aging and in AD, the permeability of the brain barriers increase. As such, a greater contact of the brain parenchyma with the blood content alters the highly controlled neural environment, which impacts on neural function. Of interest, the brain barriers are more than mere obstacles to the passage of molecules and cells, and therefore active players in brain homeostasis, which is still to be further recognized and investigated in the context of health and disease. Herein, we provide a review on how the brain barriers change during aging and in AD and how these processes impact on brain function

Stressed brain, diseased heart : a review on the pathophysiologic mechanisms of neurocardiology

Cardiovascular diseases are traditionally related to well known risk factors like dyslipidemia, smoking, diabetes and hypertension. More recently, stress, anxiety and depression have been proposed as risk factors for cardiovascular diseases including heart failure, ischemic disease, hypertension and arrhythmias. Interestingly, this association has been established largely on the basis of epidemiological data, due to insufficient knowledge on the underlying pathophysiologic mechanisms. This review will revisit evidence on the interaction between the cardiovascular and nervous systems, highlighting the perspective on how the central nervous system is involved in the pathogenesis of cardiovascular diseases. Such knowledge is likely to be of relevance for the development of better strategies to treat patients in a holistic perspective

The relevance of the brain in the diseased heart : authors' response

In their comment to our recent paper entitled “Stressed Brain, Diseases Heart: A review on the pathophysiologic mechanisms of neurocardiology.” [1], Dominguez-Rodriguez and Abreu-Gonzalez [2] emphasize the relevance of circadian rhythm in cardiovascular diseases and propose the suprachiasmatic nucleus and melatonin as key mediators in its pathophysiology. We found this a very interesting observation. The incidence of acute myocardial infarction [3] and its extension [4] displays a circadian pattern usually peaking in early morning

Telephone-based screening tools for mild cognitive impairment and dementia in aging studies : a review of validated instruments

The decline of cognitive function in old age is a great challenge for modern society. The simultaneous increase in dementia and other neurodegenerative diseases justifies a growing need for accurate and valid cognitive assessment instruments. Although in-person testing is considered the most effective and preferred administration mode of assessment, it can pose not only a research difficulty in reaching large and diverse population samples, but it may also limit the assessment and follow-up of individuals with either physical or health limitations or reduced motivation. Therefore, telephone-based cognitive screening instruments can be an alternative and attractive strategy to in-person assessments. In order to give a current view of the state of the art of telephone-based tools for cognitive assessment in aging, this review highlights some of the existing instruments with particular focus on data validation, cognitive domains assessed, administration time and instrument limitations and advantages. From the review of the literature, performed using the databases EBSCO, Science Direct and PubMed, it was possible to verify that while telephone-based tools are useful in research and clinical practice, providing a promising approach, the methodologies still need refinement in the validation steps, including comparison with either single instruments or neurocognitive test batteries, to improve specificity and sensitivity to validly detect subtle changes in cognition that may precede cognitive impairment.This work was funded by the European Commission (FP7): "SwitchBox" (Contract HEALTH-F2-2010-259772). Teresa C. Castanho and Liliana Amorim are recipients of doctoral fellowships from the Fundacao para a Ciencia e Tecnologia (FCT, Portugal) and the MyHealth project (Contract DoIT-13853), respectively. Nadine C. Santos is a recipient of a postdoctoral fellowship by the Switchbox project

Unbiased stereological method to assess proliferation throughout the subependymal zone

The subependymal zone (SEZ), frequently named as adult subventricular zone (SVZ), is a niche of adult neural stem and progenitor cells that lines a large extension of the lateral ventricles of the brain. The majority of the studies do not analyze the SEZ throughout its entire extension. Instead, studies of cell populations within the SEZ typically focus their analysis on a narrow space between specific bregma coordinates that provides a perspective of only a small portion of the SEZ. We have previously proposed a standard division for the SEZ at the anterior-posterior and dorsal-ventral axes based on external brain anatomical hallmarks (Falcao et al., PLoS One 7:e38647, 2012). Herein, we describe in detail the procedure and a stereological approach that can be used to obtain an unbiased estimation of the SEZ cell proliferation under physiological and pathological conditions. This approach takes into consideration clear SEZ anatomical divisions, both on the anterior-posterior and dorsal-ventral axes, which will standardize future studies on the SEZ

Interleukin-10: A Key Cytokine in Depression?

An increasing body of evidence implicates proinflammatory cytokines in psychiatric disorders, namely, in depression. Of notice, recent studies showed that anti-inflammatory cytokines, such as IL-10, also modulate depressive-like behavior. In this article, we propose that the anti-inflammatory cytokine IL-10 is a putative link between two of the most widely reported phenomenon observed in depressed patients: the disruption of the hypothalamic-pituitary-adrenal axis and the imbalanced production of cytokines. If so, IL-10 might represent a novel target for antidepressant therapy

Iodine status of pregnant women and their progeny in the minho region of Portugal

[Background]: Iodine sufficiency is particularly necessary throughout pregnancy, given its recognized impact on psychomotor performance of the offspring. There are no recent reports about iodine status or supplementation in Portugal, a country that the International Council for Control of Iodine Deficiency Disorders considered, in 2004, to have probably reached iodine sufficiency. The objective of this study was to evaluate in the Minho region of Portugal the iodine status of women throughout pregnancy and after delivery, and of their offspring. [Methods]: Urinary iodine concentration (UI) was determined in 78 nonpregnant premenopausal women, in 140 pregnant women in the three trimesters of pregnancy and after delivery, and in their 142 offspring. Milk iodine concentration was determined at day 3 and 3 months after delivery. The thyroid volume was determined in women in the third trimester of pregnancy and 3 months after delivery and in infants at 3 months of age. [Results]: Based on the World Health Organization criteria, both nonpregnant and pregnant women had iodine deficiency (ID), as documented by median UI of <75 μg/L and milk iodine concentration of <100 μg/L. Goiter was observed in 14% of the pregnant women. Concordant with the mother's ID, median neonatal UI was low (71 and 97 μg/L at 3 days and 3 months of age). Conclusion: Portuguese women of the Minho region have an inadequate iodine intake, which may compromise the potential for full psychomotor development of their progeny. These observations suggest that iodine supplementation should be implemented throughout pregnancy and lactation in Portugal. © Copyright 2009, Mary Ann Liebert, Inc.This study was supported by the Portuguese Science Foundation (FCT)-FEDER Grant POCTI_PSI_60948_2004 and by the Integrated Actions for exchange of scientists ‘‘Portugal-Spain E-84=2006.’’Peer Reviewe