Polymorphisms of TNF-alpha (- 308), IL-1beta (+ 3954) and IL1-Ra (VNTR) are associated to severe stage of endometriosis in Mexican women: a case control study.

BACKGROUND: Endometriosis is an estrogen-dependent and chronic inflammatory disease affecting up to 10% of women. It is the result of a combined interaction of genetic, epigenetic, environmental, lifestyle, reproductive and local inflammatory factors. In this study, we investigated whether single nucleotide polymorphisms (SNPs) mapping to TNF-alpha (TNF, rs1800629) and IL-1beta (IL1B, rs1143634) and variable number tandem repeat polymorphism mapping to IL1-Ra (IL1RN intron 2, rs2234663) genetic loci are associated with risk for endometriosis in a Mexican mestizo population. METHODS: This study included 183 women with confirmed endometriosis (ENDO) diagnosed after surgical laparoscopy and 186 women with satisfied parity and without endometriosis as controls (CTR). PCR/RFLP technique was used for genotyping SNPs (rs1800629 and rs1143634); PCR for genotyping rs2234663. RESULTS: We found no statistical differences in age between groups nor among stages of endometriosis and the CTR group. We observed no difference in genotype and allele frequencies, nor carriage rate between groups in none of the three studied polymorphisms. The prevalence of TNF*2-allele heterozygotes (p = 0.025; OR 3.8), TNF*2-allele (p = 0.029; OR 3.4), IL1B*2-allele heterozygotes (p = 0.044; OR 2.69) and its carriage rate (p = 0.041; OR 2.64) in endometriosis stage IV was higher than the CTR group. Surprisingly, the carriage rate of IL1RN*2-allele (ENDO: p = 0.0004; OR 0.4; stage I: p = 0.002, OR 0.38; stage II: p = 0.002, OR 0.35; stage III: p = 0.003, OR 0.33), as well as the IL1RN*2-allele frequencies (ENDO: p = 0.0008, OR 0.55; I: p = 0.037, OR 0.60; II: p = 0.002, OR 0.41; III: p = 0.003, OR 0.38) were lower than the CTR group. Women with endometriosis stage IV (severe) had frequencies more alike to the CTR group in the IL1RN*2 allele frequency (31.2% vs. 27.2%) and carriage rate (37.5% vs. 41.9%). CONCLUSION: Although these polymorphisms are not associated with the risk of endometriosis, Mexican mestizo women with severe stage of endometriosis have higher frequencies of TNF*2-, IL1B*2- and IL1RN*2-alleles, which may explain a possible correlation with disease severity rather than predisposition or risk.

Exposure to anandamide on young rats causes deficits in learning, temporal perception and induces changes in NMDA receptor expression.

Human use of marijuana at an early age has been reported to lead to cognitive impairment. However, researchers have not yet clearly determined whether this impairment is due to marijuana-induced alterations in the developing nervous system and whether this deficit persists into adulthood after marijuana use has ceased. We administered anandamide to developing rats to assess the effect of cannabinoids on development. We subsequently evaluated learning and performance on a temporal bisection task in adulthood and assessed the expression of genes encoding principal subunits of NMDA receptors (Grin1, Grin2A, and Grin2B) in the hippocampus and prefrontal cortex. Rats in two age groups, namely, 21-day-old and 150-day-old rats, received intraperitoneal injections of anandamide or the vehicle for 14 days. Both groups performed a temporal bisection test, which included listening to tones of different durations and classifying them as short or long. The expression of the Grin1, Grin2A and Grin2B mRNAs was evaluated using quantitative PCR in both age groups after extracting mRNA from the hippocampus and prefrontal cortex. We observed a learning impairment in the temporal bisection task (p < 0.05) and changes in the response latency (p < 0.05) in rats that received anandamide. Furthermore, these rats exhibited decreased expression of Grin2b (p = 0.001) compared to those that received the vehicle. In human subjects, the use of cannabinoids during development induces a long-term deficit, but this deficit is not observed in subjects who use cannabinoids in adulthood. Rats treated with anandamide earlier in development took longer to learn the task, suggesting that anandamide exerts a harmful effect on cognition in developing rats. Administration of anandamide during early stages of development induced deficits in learning and other cognitive processes that depend on an adequate estimation of time. The cognitive demands of the environment must be considered when evaluating the cognitive effects of cannabinoids on developing or mature brains. High cognitive demands might induce differential expression of NMDA receptors that improves cognitive capacity, overcoming altered glutamatergic function.

Simultaneous Monitoring of Wireless Electrophysiology and Memory Behavioral Test as a Tool to Study Hippocampal Neurogenesis.

Brainwaves amplitude obtained from electroencephalography (EEG) has been well-recognized as a basis for cognitive capacity, memory, and learning on animals and humans. Adult neurogenesis mechanism is also linked to memory and learning improvement. Traditionally, researchers used to assess learning and memory parameters in rodent models by behavioral tasks. Therefore, the simultaneous monitoring of behavioral changes and EEG is particularly interesting in correlating data between brain activity and task-related behaviors. However, most of the equipment required to perform both studies are either complex, expensive, or uses a wired setup network that hinders the natural animals' movement. In this study, EEG was recorded with a wireless electrophysiology device along with the execution of a novel object recognition task (NORT). The animal's behavior was monitored simultaneously by a video tracking system. Both recordings were analyzed offline by their timestamps which were synched to link EEG signals with the animal's actions. Subjects consist of adult Wistar rats after medium-term environmental enrichment treatment. Six skull screw electrodes were fixed in pairs on both hemispheres over frontal, central, and parietal regions and were referenced to an electrode located posterior of the nasal bone. NORT protocol consists of exposing the animal to two identical objects for 10 min. After 2 h and 24 h, one of the objects was replaced with a novel one. Exploration time for each object was monitored by a behavioral tracking software (BTS) and EEG data recording. The analysis of the EEG synced with behavioral data consists of estimations of alpha and beta relative band power and comparisons between novel object recognition versus familiar object exploration, between three experimental stages. In this manuscript, we have discussed electrodes manufacturing process, epidural electrodes implantation surgery, environmental enrichment protocol, NORT protocol, BTS setup, EEG - BTS coupling for simultaneous monitoring in real-time, and EEG data analysis based on automatic events detection.

Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats.

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is a meaningful concept because it is associated with psychiatric conditions in humans and with maladaptive behavior in non-human animals. It is believed that impulsivity is composed of separate factors. There are laboratory protocols devised to assess each of these factors using standardized automated equipment. Delay discounting is associated with the incapacity to be motivated by delayed outcomes. This factor is evaluated through intertemporal choice protocols, which consist of presenting the individual with a choice situation involving an immediate reward and a larger but delayed reward. Response inhibition deficit is associated with the incapacity to withhold prepotent responses. Differential reinforcement of low rates (DLR) and feature-negative discrimination protocols assess the response inhibition deficit factor of impulsivity. The former imposes a condition to a motivated individual in which most wait a minimum period of time for a response to be rewarded. The latter evaluates the capacity of individuals to refrain from food seeking responses when a signal of the absence of food is presented. The purpose of these protocols is to construct an objective quantitative measure of impulsivity, which serves to make cross-species comparisons, allowing the possibility of translational research. The advantages of these particular protocols include their easy set-up and application, which stems from the relatively small amount of equipment needed and the automated nature of these protocols.

SEXRAT MALE: A smartphone and tablet application to annotate and process live sexual behavior in male rodents.

BACKGROUND: In behavioral neuroscience studies, it is essential to accurately and easily record rodent sexual behavior. However, current systems are complex, expensive and often require a computer that hinders their use in situ. NEW METHOD: SEXRAT MALE is new software for the real-time annotation and process of live sexual behavior in male rodents. RESULTS: SEXRAT MALE works on smartphones and tablets Android™ operating system, and soon on iOS™. This software uses a simple algorithm based on chronometry and the counting of the behavioral states that the user taps on the screen. It can annotate, count and time a complex sequence of behavioral states by a human observer, such as genital exploration, mounting, intrusion, ejaculation, and up to nine wildcard events established by the user, such as rearing and female receptivity events. SEXRAT MALE reports time, order, duration, intervals, and the simple statistics of all events in the session through data files, which are easily importable from any statistical software. SEXRAT MALE showed greater precision among both expert and naïve observers analyzing sexual interaction, decreasing errors and providing greater accuracy of timing data. Additionally, it records and processes more information than the traditional recording, in terms of factors such as order, occurrence time, duration, events intervals, and other processed data. COMPARISON(S) WITH EXISTING METHOD: Compared to the traditional, manual method, SEXRAT MALE is more accurate, reliable, and simplifies the process of recording and processing. CONCLUSIONS: SEXRAT MALE provides a novel tool for accurately recording live male rodent sexual behavior.

Genetic polymorphisms of antioxidant enzymes CAT and SOD affect the outcome of clinical, biochemical, and anthropometric variables in people with obesity under a dietary intervention.

BACKGROUND: Genetic polymorphisms of antioxidant enzymes CAT, GPX, and SOD are involved in the etiology of obesity and its principal comorbidities. The aim of the present study was to analyze the effect of aforementioned SNPs over the output of several variables in people with obesity after a nutritional intervention. The study included 92 Mexican women, which received a dietary intervention by 3 months. Participants were genotyped and stratified into two groups: (1) carriers; mutated homozygous plus heterozygous (CR) and (2) homozygous wild type (WT). A comparison between CR and WT was done in clinical (CV), biochemical (BV), and anthropometric variables (AV), at the beginning and at the end of the intervention. RESULTS: Participants (n = 92) showed statistically significant differences (p < 0.05) at the end of the nutritional intervention in several CV, BV, and AV. However, two kinds of responses were observed after genotyping participants: (A) CR and WT showed statistically significant differences (p < 0.05) in several CV, BV, and AV for the SNPs 599C>T GPX1 (rs1050450), - 251A>G SOD1 (rs2070424), and - 262C>T CAT (rs1001179). (B) Only CR showed statistically changes (p < 0.05) in several CV, BV, and AV for the SNPs - 21A>T CAT (rs7943316) and 47C>T SOD2 (rs4880). The dietary intervention effect was statistically significantly between the polymorphisms of 47C>T SOD2 and BMI, SBP, TBARS, total cholesterol, and C-LCL (p < 0.05) and between the polymorphisms of - 21A>T CAT (rs7943316) and SBP, DBP, total cholesterol, and atherogenic index (p < 0.05). CONCLUSION: People with obesity display different response in several CV, BV, and AV after a nutritional intervention, depending on the antioxidant genetic background of SOD and CAT enzymes.

Hormonal State Comparison (Progesterone, Estradiol, and Leptin) of Body Fat and Body Mass Indices in Mexican Women as a Risk Factor for Neonatal Physiologic Condition.

STUDY OBJECTIVE: Describe the impact of teen pregnancy on later ovarian activity and metabolic hormones considering the concentration of current levels of ovarian steroids and leptin in a sample of Mexican females. DESIGN: Cross-sectional study in the maternity of the General Hospital of Atlacomulco and campus of the Autonomous University of the State of Mexico. PARTICIPANTS: 71 women between the ages of 18 and 24, and 160 neonates seen between March 2010 and June 2012. MAIN OUTCOME MEASURES: The measurements obtained included anthropometric body composition (bioelectrical impedance), serum hormone quantification of ovarian steroids and leptin (immunoassays), and the Apgar scores, height, and weight in neonates. Statistical analysis included ANOVA, Student, and chi-square for P < .05. RESULTS: Adolescent mothers showed significantly lower concentrations of estradiol (P = .001) and progesterone (P = .001). However, higher levels of leptin in adolescent mothers were not statistically different compared with older mothers (P = .84). Also, leptin was correlated with all measures of adiposity. The mean birth weights (P = .001) and Apgar scores (P = .001) were lower in neonates of adolescent mothers than in neonates of adult mothers. There was no association between maternal age with the anthropometric variables studied. CONCLUSIONS: Early reproduction represents a metabolic stress condition that modifies the long term ovarian activity and metabolic hormones, and impacts the morbidity-mortality of the mother and offspring in a later vital life cycle stage.

Effects on Behavior by Different Exposure Durations of Predator Scent Stress / Efectos Conductuales por Exposición a Diferentes Duraciones de Estrés por Olor de Depredador

Abstract Stress is conceptualized as a systemic response triggered by a stimulus potentially harmful to an organism. Instead of an adaptive outcome, life-threatening experiences may contribute to the development of anxiety disorders and depression. Predator scent stress (PSS) is one of the most utilized rodent models of stress-induced psychopathology, in which rodents are exposed to a volatile predator cue that signifies imminent danger. It is unclear if the duration of a life-threatening experience could have differential consequences on the expression of anxiety-like and depression-like behaviors. For this reason, the goal of this present study was to evaluate the effect of different exposure durations (3 min., 10 min., or 20 min.) to the scent of bobcat urine. Wistar rats housed under 12/12 dark cycle in standard laboratory conditions were exposed to the PSS model and 24 hrs. after the stressor, behavioral consequences were evaluated in the open field test, saccharin preference test, and forced swim test. The results obtained show that a 10-minute exposure is sufficient to induce an anxiety-like and a depression-like behavioral profile. We conclude that the time exposure could be a major variable to obtain clear and trustable results and to avoid overexposure to stressor.

Resumen El estrés es una respuesta sistémica desencadenada por un estímulo potencialmente peligroso para el organismo. Esta respuesta permite al organismo adaptarse a la condición estresante, sin embargo, experiencias que amenazan a la vida pueden incrementar el riesgo de desarrollar trastornos de ansiedad y depresión. La exposición al olor de depredador (EOD) es el modelo animal de patología inducida por estrés más utilizado. Consta de la exposición a una pista olfativa que significa peligro inminente. Aún no está claro si la duración a una experiencia que amenaza la vida puede generar diferencias en la expresión conductas tipo-ansiedad o tipo-depresión. Por esta razón, el objetivo de este estudio fue evaluar el efecto de diferentes duraciones de exposición (3 min., 10 min. o 20 min.) al aroma de lince. Se utilizaron ratas hembra de la cepa Wistar en un ciclo luz oscuridad 12/12 en condiciones estándar de laboratorio, los sujetos fueron evaluados en la prueba de campo abierto, preferencia de sacarina y nado forzado 24 hrs. después de terminado el estresor. Los resultados indican que la exposición a 10 min. es suficiente para inducir el perfil conductual tipo-depresión y tipo-ansiedad. Concluimos que el tiempo de exposición puede ser una variable de mayor importancia para obtener resultados confiables y prevenir exposiciones innecesarias al estrés.