Effects of serotonin transporter and receptor polymorphisms on depression.

INTRODUCTION: Serotonin is highly implicated in the regulation of emotional state and the execution of cognitive tasks, so much so that the serotonin transporter genes (5-HTT, SLC6A4) and the serotonin receptor genes (HTR1A, HTR1B, HTR2A) have become the perfect candidates when studying the effects that these genes and their polymorphic variations have on depression characteristics. OBJECTIVE: A review of research reports that have studied the effects of variations in the serotonin transporter and receptor genes on different clinical features of depression. METHODS: A search of the Scopus, Web of Science and PubMed databases was conducted using the keywords ("depression" AND "polymorphism"). CONCLUSIONS: According to the review of 54 articles, the short allele of the 5-HTTLPR polymorphism was found to be the most reported risk factor related to the development of depression and its severity. Variations in the genes studied (SLC6A4, HTR1A, HTR2A) can generate morphological alterations of brain structures.

Efectos de los Polimorfismos del Transportador y de los Receptores de Serotonina en la Depresión

Introducción: La serotonina tiene gran implicación en la regulación del estado emocional y la ejecución de tareas cognitivas, de modo que los genes del transportador de serotonina (5-HTT, SLC6A4) y de los receptores de serotonina (HTR1A, HTR1B, HTR2A) se convierten en candidatos adecuados para estudiar los efectos de estos genes y sus variaciones polimórficas en las características de la depresión. Objetivo: Revisión de reportes de investigación que hayan estudiado los efectos de las variantes de los genes del transportador y de los receptores de serotonina en las diferentes características clínicas de la depresión. Métodos: Se realizó una búsqueda en las bases de datos Scopus, Web of Science y PubMed con las palabras clave "depression", AND "polymorphism". Conclusiones: Según la revisión de 54 artículos, se encontró que el alelo corto del polimorfismo de 5-HTTLPR es el factor de riesgo más reportado en relación con el desarrollo de depresión y su gravedad. Las variantes de los genes estudiados (SLC6A4, HTR1A, HTR1B y HTR2A) pueden generar alteraciones morfológicas de estructuras cerebrales.

Introduction: Serotonin is highly implicated in the regulation of emotional state and the execution of cognitive tasks, so much so that the serotonin transporter genes (5-HTT, SLC6A4) and the serotonin receptor genes (HTR1A, HTR1B, HTR2A) have become the perfect candidates when studying the effects that these genes and their polymorphic variations have on depression characteristics. Objective: A review of research reports that have studied the effects of variations in the serotonin transporter and receptor genes on different clinical features of depression. Methods: A search of the Scopus, Web of Science and PubMed databases was conducted using the keywords ("depression" AND "polymorphism"). Conclusions: According to the review of 54 articles, the short allele of the 5-HTTLPR polymorphism was found to be the most reported risk factor related to the development of depression and its severity. Variations in the genes studied (SLC6A4, HTR1A, HTR2A) can generate morphological alterations of brain structures.

Perfil cognitivo y social en niños y niñas con Trastorno del Espectro Autista / Cognitive and social profile in children with autism spectrum disorder

El Trastorno del Espectro Autista (TEA) es una condición que se caracteriza por presentar fallas en la conducta social y comportamientos repetitivos. Su perfil neuropsicológico muestra hallaz-gos heterogéneos que dependen de la severidad del trastorno. El objetivo del presente trabajo es describir el funcionamiento neuropsicológico de una muestra de niños y niñas con TEA que asisten al Instituto para el Desarrollo Integral del Niño en condición de Autismo (DINA). La muestra estuvo conformada por 78 participantes, 15.4% de género femenino y 84.6% de géne-ro masculino, con edades entre los 6 y los 16 años. Los instrumentos utilizados fueron protocolo neuropsicológico adaptado de la ENI, prorrateo de inteligencia del WISC-IV, Test de Sally y Ann, Test de Expresiones faciales adaptadopor Paul Ekman y el Test de la Mirada para niños, El Test de Metidas de Pata, e Historias Extrañas de Happé. Los resultados se discuten a la luz de la li-teratura científica sobre el tema.

Autism Spectrum Disorder (ASD) is a condition that is characterized by failures in social behav-ior and repetitive behaviors. The neuropsychological profile shows heterogeneous findings that depends on the severity of the disorder. The objective of this paper is to describe the neuropsychological functioning of a sample of children with ASD who attend the Institute for the Integral Development of Children with Autism (DINA). The sample consisted of 78 partici-pants, 15.4% female and 84.6% male, aged between6 and 16 years. The instruments used were the neuropsychological protocol adapted from the ENI, intelligence apportionment from the WISC-IV, Sally and Ann Test, Facial Expressions Test adapted by Paul Ekman and Reading the Mind in the Eye for children, Faux Pas Test, and The Happé’s Strange Stories test. The re-sults are discussed considering the scientific literature on the subject. (AU)

Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets.

Infections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular pathogenesis of toxoplasmosis-related inflammation through next-generation sequencing, to assess RNA expression profiles in peripheral blood from 5 female patients with chronic toxoplasmosis and 5 healthy female controls. All plasma samples were analyzed for anti-Toxoplasma IgG and IgM antibody titers by using electrochemiluminescence. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. We evaluated the levels of INF-γ, IL-2, IL-12, TNF-α, IL-10, and IL-1ß in culture supernatants of Peripheral Blood Mononuclear Cells infected with Toxoplasma lysate antigen (TLA) prepared with tachyzoites of strain T. gondii RH. Differential expression analysis was performed using DESeq2, pathway and enrichment analysis of DEGs was done on WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and Protein-protein interaction was carried out using NetworkAnalyst with STRING. In older people with chronic asymptomatic infection, a significant difference in the levels of inflammatory cytokines INF-γ and IL-2 was observed compared to seronegative individuals. Our results revealed differences in the regulation of critical biological processes involved in host responses to chronic T. gondii infection. Gene ontology analysis revealed several biologically relevant inflammatory and immune-related pathways.

Inflammatory gene expression profiling in peripheral blood from patients with Alzheimer's disease reveals key pathways and hub genes with potential diagnostic utility: a preliminary study.

BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease caused by central nervous system disorders. Late-onset Alzheimer disease (LOAD) is the most common neurodegenerative disorder worldwide. Differences at the expression level of certain genes, resulting from either genetic variations or environmental interactions, might be one of the mechanisms underlying differential risks for developing AD. Peripheral blood genome transcriptional profiling may provide a powerful and minimally invasive tool for the identification of novel targets beyond Aß and tau for AD research. METHODS: This preliminary study explores molecular pathogenesis of LOAD-related inflammation through next generation sequencing, to assess RNA expression profiles in peripheral blood from five patients with LOAD and 10 healthy controls. RESULTS: The analysis of RNA expression profiles revealed 94 genes up-regulated and 147 down-regulated. Gene function analysis, including Gene Ontology (GO) and KOBAS-Kyoto Encyclopedia of DEGs and Genomes (KEGG) pathways indicated upregulation of interferon family (INF) signaling, while the down-regulated genes were mainly associated with the cell cycle process. KEGG metabolic pathways mapping showed gene expression alterations in the signaling pathways of JAK/STAT, chemokines, MAP kinases and Alzheimer disease. The results of this preliminary study provided not only a comprehensive picture of gene expression, but also the key processes associated with pathology for the regulation of neuroinflammation, to improve the current mechanisms to treat LOAD.

Effects of Serotonin Transporter and Receptor Polymorphisms on Depression. / Efectos de los Polimorfismos del Transportador y de los Receptores de Serotonina en la Depresión.

INTRODUCTION: Serotonin is highly implicated in the regulation of emotional state and the execution of cognitive tasks, so much so that the serotonin transporter genes (5-HTT, SLC6A4) and the serotonin receptor genes (HTR1A, HTR1B, HTR2A) have become the perfect candidates when studying the effects that these genes and their polymorphic variations have on depression characteristics. OBJECTIVE: A review of research reports that have studied the effects of variations in the serotonin transporter and receptor genes on different clinical features of depression. METHODS: A search of the Scopus, Web of Science and PubMed databases was conducted using the keywords ("depression" AND "polymorphism"). CONCLUSIONS: According to the review of 54 articles, the short allele of the 5-HTTLPR polymorphism was found to be the most reported risk factor related to the development of depression and its severity. Variations in the genes studied (SLC6A4, HTR1A, HTR2A) can generate morphological alterations of brain structures.

Cafeína y comportamiento animal. Análisis sobre condiciones experimentales / Caffeine and animal behavior. Analysis of experimental conditions

Objetivo: realizar una revisión teórica relacionada con el efecto de la cafeína en el comportamiento animal en estudios que incluyen tareas de aprendizaje, memoria y/o actividad motora, con el fin de analizar algunas condiciones experimentales. Materiales y métodos: búsqueda de artículos publicados entre los años 1995 a 2018 en las bases de datos Pubmed y Scopus por medio de la relación de palabras clave: cafeína,café, ratas, ratones, atención, memoria y aprendizaje. Se revisaron las tareas de aprendizaje y/o actividad motora, el tipo y género de cepas, así como el tratamiento con cafeína. También se incluyeron artículos de revisión de años anteriores al rango de tiempo, con el fin de ampliar el estado del arte de la cafeína y sus efectos. Resultados: mientras algunos estudios indican que la cafeína ejerce un efecto positivo sobre actividades motoras y cognitivas, otros estudios concluyen lo contrario. La variación en las condiciones experimentales de los estudios analizados puede incidir en los resultados obtenidos. Conclusión: el amplio rango de condiciones experimentales en una misma tarea de memoria no permite que se delimite el espectro de variables en los protocolos de investigación con cafeína, por ello no se logra identificar variables biológicamente importantes que, al ser identificadas, pueden convergen hacia un conjunto de procedimientos estandarizados en paradigmas específicos de aprendizaje..(AU)

Objective: the aim is realize theoretical review related to the effect of caffeine on animal behavior in studies that include task learning, memory and motor activity, with the purpose of study some experimental conditions. Materials and methods: searching of articles published since 1997-2013 in the PubMed and Scopus databases, through the relationship of keywords: caffeine, coffee, rats, mice, attention, memory and learning. The tasks of learning and/or motor activity were reviewed; the type and genus of strains, as well as the treatment with caffeine were analyzed. Results: while some studies indicate that caffeine have a positive effect on motor and cognitive activities, other studies conclude otherwise. The variation in the experimental conditions of the analyzed studies may influence the results obtained. Conclusion: the wide range of experimental conditions in the same memory task does not allow the spectrum of variables to be delineated in the caffeine research protocols, accordingly is not possible to identify biologically important variables that, when identified, may converge towards a Set of standardized procedures in specific learning paradigms..(AU)

Different brain structures exhibit the same caffeine levels after the administration of a single dose of caffeine / Estructuras encefálicas distintas muestran concentración de cafeína similar después de la administración de una dosis única

Caffeine is a highly consumed stimulant of the nervous system. Although caffeine has diverse effects on different brain functions, little is known about the specific pharmacokinetics of this substance in the brain. For instance, most studies that assessed caffeine distribution in the rat brain have only measured caffeine levels in the cortex and striatum but not in more specific brain areas. Aims: The purpose of this work was to measure the caffeine concentration in blood and different brain regions (i.e. cortex, striatum, hippocampus, cerebellum and brainstem) at different times after the administration of a single intraperitoneal dose of caffeine. Methods: Adult Wistar rats (250 to 300 gr) were injected with a single intraperitoneal dose of 30 mg/Kg of caffeine. 20, 40, 60 and 80 minutes after administration, subjects were sacrificed by decapitation and samples of plasma, cerebral cortex, striatum, hippocampus, cerebellum and brainstem were obtained. Caffeine levels in the blood and each brain structure were measured by RP-HPLC and statistical analysis was performed. Results: Caffeine levels were higher in the plasma compared to all the brain structures studied. Different brain regions displayed similar caffeine concentrations. For all brain regions, the maximal concentration levels of caffeine were reached in the first 40 minutes after caffeine administration. Conclusions: The results support previous studies that show similar caffeine concentration between cortex and striatum, but also extend the results to other brain structures. Furthermore, caffeine concentration increases similarly in the plasma and brain structures. 40, 60 and 80 minutes after administration, caffeine concentration in the blood is almost two times higher than in the brain. This suggests that the effects of caffeine on different brain functions do not depend on pharmacokinetic differences between brain areas and are rather explained by pharmacodynamics.

Antecedentes: La cafeína es el estimulante del sistema nervioso más consumido a nivel mundial. Aunque, la cafeína tiene diferentes efectos sobre las funciones cerebrales, poco se sabe acerca de su farmacocinética en el cerebro. Por ejemplo, la mayoría de estudios que evaluaron la distribución de cafeína en el cerebro de rata han medido niveles de cafeína en corteza y estriado, pero no en áreas cerebrales más específicas. Objetivo: El propósito del trabajo fue medir la concentración de cafeína en sangre y diferentes regiones encefálicas (corteza, estriado, hipocampo, cerebelo, tallo cerebral), a diferentes tiempos, después de administrar una única dosis de cafeína. Método: Ratas Wistar adultas (250-300 gr) recibieron una dosis intraperitoneal de cafeína de 30mg/Kg de peso. 20, 40 60 y 80 minutos después de la administración, los sujetos se sacrificaron por decapitación y se obtuvieron muestras de plasma, corteza cerebral, estriado, hipocampo, cerebelo y tallo cerebral. Los niveles de cafeína en plasma y estructuras encefálicas se determinaron por RP-HPLC y se realizó análisis estadístico. Resultados: Los niveles de cafeína fueron mayores en plasma que en las regiones encefálicas estudiadas. Las distintas regiones encefálicas presentaron concentraciones similares de cafeína. En todas las regiones, la mayor concentración de cafeína se obtuvo 40 minutos después de la administración de cafeína. Conclusiones: Este estudio soporta resultados previos que muestran concentraciones similares de cafeína entre la corteza y el estriado, además los extiende a otras regiones encefálicas. La concentración de cafeína aumenta similarmente en plasma y estructuras encefálicas. 40, 60 y 80 minutos después de la administración, la concentración de cafeína en plasma es casi el doble de la encontrada en el cerebro. Lo anterior sugiere que los efectos de la cafeína en distintas funciones cerebrales no dependen de diferencias farmacocinéticas entre regiones encefálicas sino que son más bien explicadas por factores farmacodinámicos.

Bases moleculares de la memoria y su relación con el aprendizaje / Molecular Basis of Memory and its Relation with Learning

El aprendizaje y la memoria son funciones cognitivas estudiadas históricamente desde diferentes campos del saber, de los cuales, podemos mencionar la filosofía, la psicología y las neurociencias. Aportes más recientes provienen de los desarrollos de las ciencias cognitivas y, de manera particular, de la antropología, la lingüística, la semiótica y la inteligencia artificial. En su conjunto, los aportes provenientes de estos diversos campos del conocimiento tienen incidencia importante en la educación. El aprendizaje se refiere al cambio permanente o no del comportamiento, de las ideas, los conceptos, los modelos mentales, los sentimientos, intereses, motivaciones derivados de la experiencia de los sujetos; por su parte, la memoria se refiere al proceso, por el cual ese conocimiento es codificado, almacenado y recordado. El aprendizaje y la memoria son esenciales para el funcionamiento adecuado, adaptación y supervivencia independiente de las diferentes especies animales. En esta revisión, en primer lugar, se presenta una breve reseña de los estudios más sobresalientes sobre aprendizaje y memoria, en términos generales se describen los tipos de aprendizaje y de memoria con relación a la naturaleza de la información y al tiempo de almacenamiento. En segundo lugar, se describen los procesos moleculares que explican el aprendizaje y la memoria implícita y finalmente se presentan algunas reflexiones generales desde el campo conceptual de la educación en relación con los desarrollos presentados en cuanto a la memoria y al aprendizaje...(AU)

Learning and memory are cognitive functions that have been historically studied from different fields of knowledge, namely, philosophy, psychology and neurosciences.Recent contributions come from developments on cognitive sciences and, particularly, anthropology, linguistics, semiotics and artificial intelligence as well. As a whole, contributions from these different fields of knowledge have an important impact on education. Learning refers to a continuous change regarding behavior, ideas, concepts, mental models, feelings, interests, and motivations that are derived from the individuals' experience, while memory encompasses the process by which knowledge is codified, stored and retrieved. Learning and memory are paramount for proper functioning, independent adaptation and survival of different animal species. On one hand, this review shows a brief overview of the most outstanding studies on learning and memory. In general terms, it describes the types of learning and memory in relation to the nature of information and storage time. On the other hand, it presents the molecular processes underlying learning and implicit memory. It finally describes some general reflections from the conceptual perspective on education in relation to the developments of memory and learning...(AU)

CARACTERIZACIÓN DE LA ESTRUCTURA SECUNDARIA DE SUBTIPOS DE LA HISTONA H1 POR DICROÍSMO CIRCULAR / CHARACTERIZATION OF THE SECONDARY STRUCTURE OF HISTONE H1 SUBTYPES BY CIRCULAR DICHROISM (CD)

Introducción: Las histonas H1 modulan la estructura y la función de la cromatina. Las células somáticas de mamífero contienen los subtipos H1º, H1a, H1b, H1c, H1d y H1e; en células germinales de testículo y en ovocito, se encuentran respectivamente H1t y H1oo. Su estructura está conformada por un dominio central globular flanqueado por los dominios N-Terminal (DNT) y C-Terminal (DCT). Objetivo: Caracterizar la estructura secundaria de subtipos de la histona H1 mediante dicroísmo circular (DC). Materiales y Métodos: La histona H1 total se extrajo de núcleos de cerebro de rata por cromatografía de intercambio catiónico; la H1º se purificó por filtración en gel y las H1a, H1b, H1c y H1e por cromatografía líquida de alta resolución de fase reversa (RF-HPLC). Los espectros de DC se realizaron en tampón fosfato 10 mM; tampón fosfato 10 mM, 20% TFE (trifluoroetanol); tampón fosfato 10 mM, 40% TFE; tampón fosfato 10 mM, 60% TFE; tampón fosfato 10 mM, 150 mM NaCl y tampón fosfato 10 mM, 1 M NaCl. El análisis de los espectros se realizó con el programa Standard Analysis. Resultados: El porcentaje de hélice-alfa se calculó por diferentes métodos matemáticos teniendo en cuenta elipticidad molar a 193 nm y a 222 nm; con programa de deconvolución K2D y con relaciones cualitativas R1 y R2. El TFE induce la estructura en hélice-alfa en cada uno de los subtipos, mientras que NaCl no induce ningún cambio importante. Conclusión: Los subtipos con mayor contenido de hélice-alfa son H1a y H1c. Las diferencias observadas en el porcentaje de hélice-alfa entre los diferentes subtipos puede ser importante para su diferenciación funcional.

H1 histones modulate the structure and function of chromatin. Mammalian somatic cells contain H1º, H1a, H1b, H1c, H1d and H1e subtypes; H1t and H1oo are found in testicular germ cells and oocyte, respectively. Its structure consists of a globular core domain flanked by N-terminal (DNT) and C-terminal (DCT) domains. Objective: To characterize the secondary structure of histone H1 subtypes through circular dichroism (CD). Materials and Methods: Total histone H1 was extracted for rat brain nuclei by cation exchange chromatography; histone H1º was purified by gel filtration and the histones H1a, H1b, H1c and H1e were purified by reversed phase high performance liquid chromatography (RP-HPLC). CD spectra were performed in 10 mM phosphate buffer; 10 mM, 20% TFE phosphate buffer (trifluoroethanol); 10 mM, 40% TFE; phosphate buffer 10 mM, 60% TFE; phosphate buffer 10 mM, 150 mM NaCl and phosphate buffer 10 mm, 1 M NaCl. The analysis of the spectra was performed with JASCO Standard Analysis. Results: The percentage of alpha-helix was calculated using different mathematical methods, taking into account the molar ellipticity at 193 nm, and 222 nm, with K2D deconvolution program and the R1 and R2 qualitative relationships. The results indicate that TFE induced the alpha-helix structure in each of the subtypes, whereas NaCl did not induce any significant change. Conclusion: H1a and H1c are subtypes with highest content of alpha-helix. The observed differences in the percentage of alpha-helix between different subtypes may be important for their functional differentiation.

Porphyromonas gingivalis y enfermedades sistémicas / Porphyromonas gingivalis and systemic diseases

Resumen Porphyromonas gingivalis (P.g.) es un cocobacilo Gram negativo que habita el surco gingival. Sus factores patogénicos estructurales como las fimbrias facilitan su adhesión al tejido, mientras que factores de secreción como proteasas y hialuronidasas hidrolizan componentes del tejido periodontal, causando daño tisular y pérdida de soporte dentario. Algunos componentes estructurales de Porphyromonas como los lipopolisacáridos se han asociado a enfermedades sistémicas. En esta revisión se presenta una descripción de los factores patogénicos de Porphyromonas gingivalis y su relación con enfermedad pulmonar, ateroesclerosis y parto pretérmino, haciendo énfasis en los mecanismos moleculares de dicha asociación.

Abstract Porphyromonas gingivalis (P.g.) is a gram-negative coccobacillus that resides in the gingival sulcus. Some of its structural pathogenic factors like fimbriae allow its adhesion to the tissues of the gingival sulcus, where P.g. secretes proteases and hyaluronidases that hydrolyze components of the periodontal tissues, leading to tissue damage and loss of teeth support. Some bacterial components such as lipopolysaccharides have been associated with systemic diseases. This review focuses on the molecular mechanisms linking the pathogenic factors of Porphyromonas gingivalis to diseases such as atherosclerosis, pulmonary disease and preterm birth.