Estrogens, brain and behavior: studies in fundamental neurobiology and observations related to women's health

Mechanisms and consequences of the effects of estrogen on the brain have been studied both at the fundamental level and with therapeutic applications in mind. Estrogenic hormones binding in particular neurons in a limbic-hypothalamic system and their effects on the electrophysiology and molecular biology of medial hypothalamic neurons were central in establishing the first circuit for a mammalian behavior, the female-typical mating behavior, lordosis. Notably, the ability of estradiol to facilitate transcription from six genes whose products are important for lordosis behavior proved that hormones can turn on genes in specific neurons at specific times, with sensible behavioral consequences. The use of a gene knockout for estrogen receptor alpha (ERalpha) revealed that homozygous mutant females simply would not do lordosis behavior and instead were extremely aggressive, thus identifying a specific gene as essential for a mammalian social behavior. In dramatic contrast, ERbeta knockout females can exhibit normal lordosis behavior. With the understanding, in considerable mechanistic detail, of how the behavior is produced, now we are also studying brain mechanisms for the biologically adaptive influences which constrain reproductive behavior. With respect to cold temperatures and other environmental or metabolic circumstances which are not consistent with successful reproduction, we are interested in thyroid hormone effects in the brain. Competitive relations between two types of transcription factors - thyroid hormone receptors and estrogen receptors have the potential of subserving the blocking effects of inappropriate environmental circumstances on female reproductive behaviors. TRs can compete with ERalpha both for DNA binding to consensus and physiological EREs and for nuclear coactivators. In the presence of both TRs and ERs, in transfection studies, thyroid hormone coadministration can reduce estrogen-stimulated transcription. These competitive relations apparently have behavioral consequences, as thyroid hormones will reduce lordosis, and a TRbeta gene knockout will increase it. In sum, we not only know several genes that participate in the selective control of this sex behavior, but also, for two genes, we know the causal routes. Estrogenic hormones are also the foci of widespread attention for their potential therapeutic effects improving, for example, certain aspects of mood and cognition. The former has an efficient animal analog, demonstrated by the positive effects of estrogen in the Porsolt forced swim test. The latter almost certainly depends upon trophic actions of estrogen on several fundamental features of nerve cell survival and growth. The hypothesis is raised that the synaptic effects of estrogens are secondary to the trophic actions of this type of hormone in the nucleus and nerve cell body.

NEONATAL HANDLING AND THE MATERNAL ODOR PREFERENCE IN RAT PUPS: INVOLVEMENT OF MONOAMINES AND CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN PATHWAY IN THE OLFACTORY BULB

Early-life environmental events, such as the handling procedure, can induce long-lasting alterations upon several behavioral and neuroendocrine systems. However, the changes within the pups that could be causally related to the effects in adulthood are still poorly understood. In the present study, we analyzed the effects of neonatal handling on behavioral (maternal odor preference) and biochemical (cyclic AMP response element-binding protein (CREB) phosphorylation, noradrenaline (NA), and serotonin (5-HT) levels in the olfactory bulb (OB)) parameters in 7-day-old male and female rat pups. Repeated handling (RH) abolished preference for the maternal odor in female pups compared with nonhandled (NH) and the single-handled (SH) ones, while in RH males the preference was not different than NH and SH groups. In both male and female pups, RH decreased NA activity in the OB, but 5-HT activity increased only in males. Since preference for the maternal odor involves the synergic action of NA and 5-HT in the OB, the maintenance of the behavior in RH males could be related to the increased 5-HT activity, in spite of reduction in the NA activity in the OB. RH did not alter CREB phosphorylation in the OB of both male and females compared with NH pups. The repeated handling procedure can affect the behavior of rat pups in response to the maternal odor and biochemical parameters related to the olfactory learning mechanism. Sex differences were already detected in 7-day-old pups. Although the responsiveness of the hypothalamic-pituitary-adrenal axis to stressors is reduced in the neonatal period, environmental interventions may impact behavioral and biochemical mechanisms relevant to the animal at that early age. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Comparison of biological behavior between early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix

Objectives: (1) To compare the anatomopathological variables and recurrence rates in patients with early-stage adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix; (2) to identify the independent risk factors for recurrence. Study design: This historical cohort study assessed 238 patients with carcinoma of the uterine cervix (113 and IIA), who underwent radical hysterectomy with pelvic lymph node dissection between 1980 and 1999. Comparison of category variables between the two histological types was carried out using the Pearson`s X-2 test or Fisher exact test. Disease-free survival rates for AC and SCC were calculated using the Kaplan-Meier method and the curves were compared using the log-rank test. The Cox proportional hazards model was used to identify the independent risk factors for recurrence. Results: There were 35 cases of AC (14.7%) and 203 of SCC (85.3%). AC presented lower histological grade than did SCC (grade 1: 68.6% versus 9.4%; p < 0.001), lower rate of lymphovascular space involvement (25.7% versus 53.7%; p = 0.002), lower rate of invasion into the middle or deep thirds of the uterine cervix (40.0% versus 80.8%; p < 0.001) and lower rate of lymph node metastasis (2.9% versus 16.3%; p = 0.036). Although the recurrence rate was lower for AC than for SCC (11.4% versus 15.8%), this difference was not statistically significant (p = 0.509). Multivariate analysis identified three independent risk factors for recurrence: presence of metastases in the pelvic lymph nodes, invasion of the deep third of the uterine cervix and absence of or slight inflammatory reaction in the cervix. When these variables were adjusted for the histological type and radiotherapy status, they remained in the model as independent risk factors. Conclusion: The AC group showed less aggressive histological behavior than did the SCC group, but no difference in the disease-free survival rates was noted. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

Identification of genes associated with local aggressiveness and metastatic behavior in soft tissue tumors

Soft tissue tumors represent a group of neoplasia with different histologic and biological presentations varying from benign, locally confined to very aggressive and metastatic tumors. The molecular mechanisms responsible for such differences are still unknown. The understanding of these molecular alterations mechanism will be critical to discriminate patients who need systemic treatment from those that can be treated only locally and could also guide the development of new drugs` against this tumors. Using 102 tumor samples representing a large spectrum of these tumors, we performed expression profiling and defined differentially expression genes that are likely to be involved in tumors that are locally aggressive and in tumors with metastatic potential. We described a set of 12 genes (SNRPD3, MEGF9, SPTAN-1, AFAP1L2, ENDOD1, SERPIN5, ZWINTAS, TOP2A, UBE2C, ABCF1, MCM2, and ARL6IP5) showing opposite expression when these two conditions were compared. These genes are mainly related to cell-cell and cell-extracellular matrix interactions and cell proliferation and might represent helpful tools for a more precise classification and diagnosis as well as potential drug targets.

Maternal correlates of maternal child feeding practices: a systematic review.

Establishing healthy eating habits early in life is one important strategy to combat childhood obesity. Given that early maternal child feeding practices have been linked to child food intake and weight, identifying the maternal correlates of maternal child feeding practices is important in order to understand the determinants of childhood obesity; this was the overall aim of the current review. Academic databases were searched for studies examining the relationship between maternal child feeding practices and parenting, personal characteristics and psychopathology of mothers with preschoolers. Papers were limited to those published in English, between January 2000 and June 2012. Only studies with mothers of normally developing children between the ages of 2 and 6 years were included. There were no restrictions regarding the inclusion of maternal nationality or socioeconomic status (SES). Seventeen eligible studies were sourced. Information on the aim, sample, measures and findings of these was summarised into tables. The findings of this review support a relationship between maternal controlling parenting, general and eating psychopathology, and SES and maternal child feeding practices. The main methodological issues of the studies reviewed included inconsistency in measures of maternal variables across studies and cross-sectional designs. We conclude that the maternal correlates associated with maternal child feeding practices are complex, and the pathways by which maternal correlates impact these feeding practices require further investigation.

The influence of mindfulness meditation on angry emotions and violent behavior on Thai technical college students

Introduction: Violence among technical college students is a significant issue in Thailand, South East Asia, and yet few interventions are available for use with this group. In this study the outcomes of a culturally appropriate intervention, mindfulness meditation (MM), on anger and violent behavior are reported. The MM intervention was delivered over three consecutive weeks to technical college students (n = 40) and the effects compared to a comparison group (n = 56) who attend classes as usual. Methods: Both the intervention and comparison group completed a series of validated self-report measures on aggressive and violent behavior perpetration and victimization on three occasions (pre-intervention, 1 month and 3 month post-intervention). Results: Program participants reported lower levels of anger expression at one month follow-up, but there were no observed group. ×. time interactions for self-reported violent behavior. Rates of victimization changed over time, with one interaction effect observed for reports of being threatened. Conclusions: MM may have the potential to improve emotional self-control, but is likely to only impact on violent behavior when this is anger mediated.

Reported and observed controlling feeding practices predict child eating behavior after 12 months

BACKGROUND: Controlling feeding practices are linked to children's self-regulatory eating practices and weight status. Maternal reports of controlling feeding practices are not always significantly related to independently rated mealtime observations. However, prior studies only assessed 1 mealtime observation, which may not be representative of typical mealtime settings or routines. OBJECTIVES: The first aim was to examine associations between reported and observed maternal pressure to eat and restriction feeding practices at baseline (T1) and after ∼12 mo (T2). The second aim was to evaluate relations between maternal and child factors [e.g., concern about child weight, child temperament, child body mass index (BMI)-for-age z scores (BMIz)] at T1 and reported and observed maternal pressure to eat and restriction feeding practices (T1 and T2). The third aim was to assess prospective associations between maternal feeding practices (T1) and child eating behaviors (T2) and child BMIz (T2). METHODS: A sample of 79 mother-child dyads in Victoria, Australia, participated in 2 lunchtime home observations (T1 and T2). BMI measures were collected during the visits. Child temperament, child eating behaviors, maternal parenting styles, and maternal feeding practices were evaluated at T1 and T2 via questionnaires. Associations were assessed with Pearson's correlation coefficients, paired t tests, and hierarchical regressions. RESULTS: Reported restriction (T1) was inversely associated with observed restriction at T1 (r = -0.24, P < 0.05). Reported pressure to eat (T2) was associated with observed pressure to eat (T2) (r = 0.48, P < 0.01) but only for mothers of girls. Maternal weight concern was associated with reported restriction at T1 (r = 0.29, P < 0.01) and T2 (r = 0.36, P < 0.01), whereas observed restriction (T1) was prospectively associated child BMI at T2 (β = -0.18, P < 0.05). CONCLUSIONS: Maternal reports may not always reflect feeding practices performed during mealtimes; it is possible some mothers may not be aware of their practices or observations may not capture covert controlling strategies.

Self-reported risk-taking behavior during matched-frequency sessions of alcohol versus combined alcohol and energy drinks consumption: Does co-ingestion increase risk-taking?

Background: Emerging evidence indicates that consumers of alcohol mixed with energy drink (AmED) self-report lower odds of risk-taking after consuming AmED versus alcohol alone. However, these studies have been criticized for failing to control for relative frequency of AmED versus alcohol-only consumption sessions. These studies also do not account for quantity of consumption and general alcohol-related risk-taking propensity. The aims of the present study were to (i) compare rates of risk-taking in AmED versus alcohol sessions among consumers with matched frequency of use and (ii) identify consumption and person characteristics associated with risk-taking behavior in AmED sessions. Methods: Data were extracted from 2 Australian community samples and 1 New Zealand community sample of AmED consumers (n = 1,291). One-fifth (21%; n = 273) reported matched frequency of AmED and alcohol use. Results: The majority (55%) of matched-frequency participants consumed AmED and alcohol monthly or less. The matched-frequency sample reported significantly lower odds of engaging in 18 of 25 assessed risk behaviors in AmED versus alcohol sessions. Similar rates of engagement were evident across session type for the remaining behaviors, the majority of which were low prevalence (reported by <15%). Regression modeling indicated that risk-taking in AmED sessions was primarily associated with risk-taking in alcohol sessions, with increased average energy drink (ED) intake associated with certain risk behaviors (e.g., being physically hurt, not using contraception, and driving while over the legal alcohol limit). Conclusions: Bivariate analyses from a matched-frequency sample align with past research showing lower odds of risk-taking behavior after AmED versus alcohol consumption for the same individuals. Multivariate analyses showed that risk-taking in alcohol sessions had the strongest association with risk-taking in AmED sessions. However, hypotheses of increased risk-taking post-AmED consumption were partly supported: Greater ED intake was associated with increased likelihood of specific behaviors, including drink-driving, sexual behavior, and aggressive behaviors in the matched-frequency sample after controlling for alcohol intake and risk-taking in alcohol sessions. These findings highlight the need to consider both personal characteristics and beverage effects in harm reduction strategies for AmED consumers.

Obesity prevention in early life: an opportunity to better support the role of Maternal and Child Health Nurses in Australia

BACKGROUND: Because parents with young children access primary health care services frequently, a key opportunity arises for Maternal and Child Health (MCH) nurses to actively work with families to support healthy infant feeding practices and lifestyle behaviours. However, little is known regarding the extent to which MCH nurses promote obesity prevention practices and how such practices could be better supported. METHODS: This mixed methods study involved a survey of 56 MCH nurses (response rate 84.8 %), 16 of whom participated in semi-structured qualitative interviews. Both components aimed to examine the extent to which nurses addressed healthy infant feeding practices, healthy eating, active play and limiting sedentary behavior during routine consultations with young children 0-5 years. Key factors influencing such practices and how they could be best supported were also investigated. All data were collected from September to December 2013. Survey data were analysed descriptively and triangulated with qualitative interview findings, the analysis of which was guided by grounded theory principles. RESULTS: Although nurses reported measuring height/length and weight in most consultations, almost one quarter (22.2 %) reported never/rarely using growth charts to identify infants or children at risk of overweight or obesity. This reflected a reluctance to raise the issue of weight with parents and a lack of confidence in how to address it. The majority of nurses reported providing advice on aspects of infant feeding relevant to obesity prevention at most consultations, with around a third (37 %) routinely provided advice on formula preparation. Less than half of nurses routinely promoted active play and only 30 % discussed limiting sedentary behaviour such as TV viewing. Concerns about parental receptiveness and maintaining rapport were key barriers to more effective implementation. CONCLUSION: While MCH nurses are well placed to address obesity prevention in early life, there is currently a missed public health opportunity. Improving nurse skills in behaviour change counseling will be key to increasing their confidence in raising sensitive lifestyle issues with parents to better integrate obesity prevention practices into normal MCH service delivery.

Adult partner preference and sexual behavior of male rats exposed prenatally to betamethasone

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Partial HELLP Syndrome: maternal and perinatal outcome

CONTEXTO: A síndrome HELLP é uma grave complicação da gestação caracterizada por hemólise, elevação das enzimas hepáticas e plaquetopenia. Algumas gestantes desenvolvem somente uma ou duas dessas características da síndrome HELLP. Esse quadro é denominado de síndrome HELLP parcial (SHP). OBJETIVO: O objetivo deste estudo foi avaliar as repercussões maternas e perinatais das mulheres que desenvolveram SHP e comparar os resultados com mulheres que tiveram hipertensão gestacional ou pré-eclâmpsia sem alterações dos exames laboratoriais para síndrome HELLP. TIPO DE ESTUDO: Observacional, retrospectivo e analítico. LOCAL: Maternidade do Hospital das Clínicas da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, Brasil. AMOSTRA: Foram selecionadas gestantes ou puérperas que tiveram elevação dos níveis pressóricos detectada pela primeira vez após a primeira metade da gestação com ou sem proteinúria entre janeiro/1990 a dezembro/1995. As mulheres foram divididas em dois grupos: Grupo SHP quando as mulheres com hipertensão arterial tinham pelo menos uma, mas não todas as alterações de exames que demonstravam hemólise, elevação das enzimas hepáticas ou plaquetopenia e Grupo Hipertensas pacientes com hipertensão sem alterações nos exames laboratoriais para síndrome HELLP. PRINCIPAIS VARIÁVEIS: Analisamos idade materna, raça, paridade, classificação da hipertensão, idade gestacional no diagnóstico da SHP, alterações nos exames laboratoriais para síndrome HELLP, tempo de permanência no hospital, complicações maternas, via de parto, incidência de prematuridade, restrição de crescimento intra-uterino, natimortos e neomortos. RESULTADOS: 318 mulheres foram selecionadas, das quais 41 (12,9%) tiveram SHP e 277 (87,1%) não desenvolveram alterações dos exames laboratoriais que compõem o diagnóstico da síndrome HELLP. A pré-eclâmpsia foi um tipo de hipertensão mais freqüente no grupo SHP que no grupo hipertensas. Não houve pacientes com hipertensão crônica isolada que desenvolveram SHP. A taxa de cesárea, eclâmpsia e de partos prematuros foi significativamente mais freqüente no grupo SHP que no grupo hipertensas. CONCLUSÃO: Observamos uma conduta agressiva nas pacientes com SHP, que resultou na interrupção imediata da gestação, com elevada taxa de cesárea e de recém-nascido pré-termo. Esta conduta deve ser revista para a redução desses índices.

Sexual behavior, neuroendocrine, and neurochemical aspects in male rats exposed prenatally to stress

The present study was designed to examine some short- and long-term effects of maternal restraint stress-during the period of sexual brain differentiation-on reproductive and endocrine systems, sexual behavior, and brain neurotransmitters in male rat descendants. Pregnant rats were exposed to restraint stress for 1 h/day from gestational days (GDs) 18 to 22. Prenatal stress did not influence the wet weight of sexual organs and the quantity of germ cells in adult male pups; however, these animals showed reduced testosterone levels, delayed latency to the first mount and first intromission, and also decreased number of ejaculations. Additionally, there was an increase in the dopamine and serotonin levels in the striatum. Our results indicate that prenatal stress had a long-term effect on neurotransmitter levels and sexual behavior. In this sense, reproductive problems caused by injuries during the fetal period can compromise the later success of mating as well as the capacity to generate descendants. (C) 2004 Elsevier B.V. All rights reserved.

Colony defensive behavior by the social wasp Polybia (Trichothorax) sericea (Hymenoptera, Vespidae)

This work aimed at evaluating the aggressive response of Polybia sericea, incited by mechanical means, as well as collecting information on the biological and population parameters of this species in Caatinga environments. There were positive correlations (P < 0.05) between the number of aggressors and the number of eggs, larvae and adults present in the nests. These results showed that the magnitude of the defense response exhibited by P. sericea is proportional to the energetic investment carried out by the colony in making young forms. The positive significant correlation between the number of aggressors and the total number of adults of the colony corroborates the hypothesis that colonies with a large population of adults have greater potential to perform what is called defensive altruism.

Nest defense behavior against ant attacks in post-emergent colonies of wasp Mischocyttarus cerberus (Hymenoptera, Vespidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)