Brain and circulating steroids in an electric fish: Relevance for non-breeding aggression.

Steroids play a crucial role in modulating brain and behavior. While traditionally it is thought that the brain is a target of sex steroids produced in endocrine glands (e.g. gonads), the brain itself produces steroids, known as neurosteroids. Neurosteroids can be produced in regions involved in the regulation of social behaviors and may act locally to regulate social behaviors, such as reproduction and aggression. Our model species, the weakly electric fish Gymnotus omarorum, displays non-breeding aggression in both sexes. This is a valuable natural behavior to understand neuroendocrine mechanisms that differ from those underlying breeding aggression. In the non-breeding season, circulating sex steroid levels are low, which facilitates the study of neurosteroids. Here, for the first time in a teleost fish, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify a panel of 8 steroids in both plasma and brain to characterize steroid profiles in wild non-breeding adult males and females. We show that: 1) systemic steroid levels in the non-breeding season are similar in both sexes, although only males have detectable circulating 11-ketotestosterone, 2) brain steroid levels are sexually dimorphic, as females display higher levels of androstenedione, testosterone and estrone, and only males had detectable 11-ketotestosterone, 3) systemic androgens such as androstenedione and testosterone in the non-breeding season are potential precursors for neuroestrogen synthesis, and 4) estrogens, which play a key role in non-breeding aggression, are detectable in the brain (but not the plasma) in both sexes. These data are consistent with previous studies of G. omarorum that show non-breeding aggression is dependent on estrogen signaling, as has also been shown in bird and mammal models. Overall, our results provide a foundation for understanding the role of neurosteroids, the interplay between central and peripheral steroids and potential sex differences in the regulation of social behaviors.

Neuroendocrine Mechanisms Underlying Non-breeding Aggression: Common Strategies Between Birds and Fish.

Aggression is an adaptive behavior that plays an important role in gaining access to limited resources. Aggression may occur uncoupled from reproduction, thus offering a valuable context to further understand its neural and hormonal regulation. This review focuses on the contributions from song sparrows (Melospiza melodia) and the weakly electric banded knifefish (Gymnotus omarorum). Together, these models offer clues about the underlying mechanisms of non-breeding aggression, especially the potential roles of neuropeptide Y (NPY) and brain-derived estrogens. The orexigenic NPY is well-conserved between birds and teleost fish, increases in response to low food intake, and influences sex steroid synthesis. In non-breeding M. melodia, NPY increases in the social behavior network, and NPY-Y1 receptor expression is upregulated in response to a territorial challenge. In G. omarorum, NPY is upregulated in the preoptic area of dominant, but not subordinate, individuals. We hypothesize that NPY may signal a seasonal decrease in food availability and promote non-breeding aggression. In both animal models, non-breeding aggression is estrogen-dependent but gonad-independent. In non-breeding M. melodia, neurosteroid synthesis rapidly increases in response to a territorial challenge. In G. omarorum, brain aromatase is upregulated in dominant but not subordinate fish. In both species, the dramatic decrease in food availability in the non-breeding season may promote non-breeding aggression, via changes in NPY and/or neurosteroid signaling.

A Teleost Fish Model to Understand Hormonal Mechanisms of Non-breeding Territorial Behavior.

Aggressive behaviors occurring dissociated from the breeding season encourage the search of non-gonadal underlying regulatory mechanisms. Brain estrogen has been shown to be a key modulator of this behavior in bird and mammal species, and it remains to be understood if this is a common mechanism across vertebrates. This review focuses on the contributions of Gymnotus omarorum, the first teleost species in which estrogenic modulation of non-breeding aggression has been demonstrated. Gymnotus omarorum displays year-long aggression, which has been well characterized in the non-breeding season. In the natural habitat, territory size is independent of sex and determined by body size. During the breeding season, on the other hand, territory size no longer correlates to body size, but rather to circulating estrogens and gonadosomatic index in females, and 11-ketotestosterone in males. The hormonal mechanisms underlying non-breeding aggression have been explored in dyadic encounters in lab settings. Males and females display robust aggressive contests, whose outcome depends only on body size asymmetry. This agonistic behavior is independent of gonadal hormones and fast acting androgens. Nevertheless, it is dependent on fast acting estrogenic action, as acute aromatase blockers affect aggression engagement, intensity, and outcome. Transcriptomic profiling in the preoptic area region shows non-breeding individuals express aromatase and other steroidogenic enzyme transcripts. This teleost model reveals there is a role of brain estrogen in the control of non-breeding aggression which seems to be common among distant vertebrate species.

Seasonal and social factors associated with spacing in a wild territorial electric fish.

In this study, we focused on the seasonal variation of the determinants of territory size in the weakly electric fish Gymnotus omarorum. This species is a seasonal breeder that displays year-round territorial aggression. Female and male dyads exhibit indistinguishable non-breeding territorial agonistic behavior and body size is the only significant predictor of contest outcome. We conducted field surveys across seasons that included the identification of individual location, measurements of water physico-chemical variables, characterization of individual morphometric and physiological traits, and their correlation to spatial distribution. G. omarorum tolerates a wide range of dissolved oxygen concentration, and territory size correlated positively with dissolved oxygen in both seasons. In the non-breeding season, territory size was sexually monomorphic and correlated only with body size. In the breeding season, territory size no longer correlated with body size but differed between sexes: (i) the overall spatial arrangement was sexually biased, (ii) territory size depended on gonadal hormones in both sexes, which was expected for males, but not previously reported in females, (iii) female territory size showed a positive relationship with gonadal size, and (iv) females showed relatively larger territories than males. This study demonstrates seasonal changes in the determinants of territory size and thus contributes to the understanding of the mechanisms underlying the behavioral plasticity natural territorial behavior.

The estrogenic pathway modulates non-breeding female aggression in a teleost fish.

Aggressive behaviors are widespread among animals and are critical in the competition for resources. The physiological mechanisms underlying aggression have mostly been examined in breeding males, in which gonadal androgens, acting in part through their aromatization to estrogens, have a key role. There are two alternative models that contribute to further understanding hormonal mechanisms underlying aggression: aggression displayed in the non-breeding season, when gonadal steroids are low, and female aggression. In this study we approach, for the first time, the modulatory role of estrogens and androgens upon non-breeding aggression in a wild female teleost fish. We characterized female aggression in the weakly electric fish Gymnotus omarorum and carried out acute treatments 1 h prior to agonistic encounters in dyads treated with either an aromatase inhibitor or an antagonist of androgen receptors. Anti-androgen treatment had no effect on behavior whereas acute aromatase inhibition caused a strong distortion of aggressive behavior. Territorial non-breeding aggression was robust and depended on rapid estrogen actions to maintain high levels of aggression, and ultimately reach conflict resolution from which dominant/subordinate status emerged. Our results, taken together with our own reports in males and the contributions from non-breeding aggression in bird and mammal models, suggest a common strategy involving fast-acting estrogens in the control of this behavior across species. In addition, further analysis of female non-breeding aggression may shed light on potential sexual differences in the fine tuning of social behaviors.

Biopsias percutáneas en pacientes jóvenes menores de 35 años: correlación anátomo-radiológica / Percutaneous biopsies in young patients under 35 years of age: radiological-anatomical correlation

Introducción El cáncer de mama es el más frecuente en mujeres, aunque es de baja incidencia en pacientes jóvenes. Objetivos Analizar retrospectivamente las biopsias realizadas en pacientes menores de 35 años, en el Grupo Médico Rostagno en el período comprendido entre enero de 2010 y enero de 2015, clasificarlas según edad, presentación clínica e imagenológica y realizar una correlación anátomo-radiológica. Material y método Se estudiaron 381 biopsias realizadas a pacientes de hasta 35 años en el período comprendido entre enero de 2010 y enero de 2015. Resultados La mayoría de las biopsias ­247(66%)­ se realizaron en pacientes mayores de 30 años. Únicamente 28 (8%) fueron clínicamente palpables. Sobre el total, 328 (89%) correspondieron a lesiones nodulares diagnosticadas por ecografía, según categoría bi-rads; 187 (50%) se clasificaron bi-rads 4. Por otra parte, 301 (81%) fueron core biopsia bajo guía ecográfica. Únicamente 20 (5%) fueron malignas, y el carcinoma más frecuente fue el Carcinoma Ductal Infiltrante (55%). Conclusiones Las pacientes jóvenes presentan, en su mayoría, lesiones nodulares, con una baja incidencia de lesiones malignas. La lesión maligna más frecuente fue el Carcinoma Ductal Infiltrante tipo nos de alto grado histológico

Introduction Breast cancer is the most frequent in women, although it is of low incidence in young patients. Objectives To analyze retrospectively biopsies performed in patients under 35 years of age, classify them according to age, clinical and imaging presentation and perform an anatomo-radiological correlation. Materials and method We studied 381 biopsies performed on patients up to 35 years of age in the period between January 2010 and January 2015. Results The majority of biopsies 247 (66%) were performed in patients older than 30 years, only 28 (8%) were clinically palpable. 328 (89%) corresponded to nodular lesions, diagnosed by ultrasound, according to bi-rads category 187 (50%) were classified bi-rads 4. 301 (81%) were Core biopsy under ultrasound guidance. Only 20 (5%) were malignant, and the most frequent carcinoma was Infiltrating Ductal Carcinoma (55%). Conclusions Young patients have mostly nodular lesions, with a low incidence of malignant lesions. The most frequent malignant lesion was nos type Infiltrating Ductal Carcinoma of high histological grade

Building the case for a novel teleost model of non-breeding aggression and its neuroendocrine control.

In vertebrates, aggression has been traditionally associated with high levels of circulating androgens in breeding males. Nevertheless, the centrality of androgens as primary modulators of aggression is being reconsidered in at least in two particular cases: (1) territorial aggression outside the breeding season, and (2) aggression by females. We are developing the weakly electric fish, Gymnotus omarorum, as a novel, advantageous model system to address these two alternative forms of aggression. This species displays a short, escalated contest, after which a clear hierarchical status emerges. Subordination of individuals involves three sequential decisions: interruptions of their electric discharges, retreats, and chirps. These decisions are influenced by both size asymmetry between contenders and aggression levels of dominants. Both females and males are aggressive, and do not differ in fighting ability nor in the value placed on the resource. Aggression is completely independent of gonadal hormones: dominance status is unrelated to circulating androgen and estrogen levels, and gonadectomy in males does not affect aggression. Nevertheless, estrogenic pathways participate in the modulation of this non-breeding aggression. Our results parallel those put forth in other taxa, heightening the value of G. omarorum as a model to identify commonalities in neuroendrocrine strategies of vertebrate aggression control.

Neuromodulation of the agonistic behavior in two species of weakly electric fish that display different types of aggression.

Agonistic behavior has shaped sociality across evolution. Though extremely diverse in types of displays and timing, agonistic encounters always follow the same conserved phases (evaluation, contest and post-resolution) and depend on homologous neural circuits modulated by the same neuroendocrine mediators across vertebrates. Among neuromodulators, serotonin (5-HT) is the main inhibitor of aggression, and arginine vasotocin (AVT) underlies sexual, individual and social context differences in behavior across vertebrate taxa. We aim to demonstrate that a distinct spatio-temporal pattern of activation of the social behavior network characterizes each type of aggression by exploring its modulation by both the 5-HT and AVT systems. We analyze the neuromodulation of aggression between the intermale reproduction-related aggression displayed by the gregarious Brachyhypopomus gauderio and the non-breeding intrasexual and intersexual territorial aggression displayed by the solitary Gymnotus omarorum. Differences in the telencephalic activity of 5-HT between species were paralleled by a differential serotonergic modulation through 1A receptors that inhibited aggression in the territorial aggression of G. omarorum but not in the reproduction-related aggression of B. gauderio. AVT injection increased the motivation towards aggression in the territorial aggression of G. omarorum but not in the reproduction-related aggression of B. gauderio, whereas the electric submission and dominance observed in G. omarorum and B. gauderio, respectively, were both AVT-dependent in a distinctive way. The advantages of our model species allowed us to identify precise target areas and mechanisms of the neuromodulation of two types of aggression that may represent more general and conserved strategies of the control of social behavior among vertebrates.

Differential serotonergic modulation of two types of aggression in weakly electric fish.

Agonistic aggression has provided an excellent framework to study how conserved circuits and neurochemical mediators control species-specific and context-dependent behavior. The principal inhibitory control upon aggression is serotonin (5-HT) dependent, and the activation of 5-HT(1A) receptors is involved in its action. To address whether the serotonergic system differentially regulates different types of aggression, we used two species of weakly electric fish: the solitary Gymnotus omarorum and the gregarious Brachyhypopomus gauderio, which display distinctive types of aggression as part of each species' natural behavioral repertoire. We found that in the reproduction-related aggression displayed by B. gauderio after conflict resolution, the serotonergic activity follows the classic pattern in which subordinates exhibit higher 5-HT levels than controls. After the territorial aggression displayed by G. omarorum, however, both dominants and subordinates show lower 5-HT levels than controls, indicating a different response of the serotonergic system. Further, we found interspecific differences in basal serotonin turnover and in the dynamic profile of the changes in 5-HT levels from pre-contest to post-contest. Finally, we found the expected reduction of aggression and outcome shift in the territorial aggression of G. omarorum after 8-OH-DPAT (5-HT(1A) receptor agonist) administration, but no effect in the reproduction-related aggression of B. gauderio. Our results demonstrate the differential participation of the serotonergic system in the modulation of two types of aggression that we speculate may be a general strategy of the neuroendocrine control of aggression across vertebrates.