Sexually size dimorphic brains and song complexity in passerine birds

Neural correlates of bird song involve the volume of particular song nuclei in the brain that govern song development, production, and perception. Intra- and interspecific variation in the volume of these song nuclei are associated with overall brain size, suggesting that the integration of complex songs into the brain requires general neural augmentation. In a comparative study of passerine birds based on generalized least square models, we tested this hypothesis by exploring the interspecific relationship between overall brain size and repertoire size. We found no significant association between song complexity of males and brain size adjusted for body size. However, species in which males produced complex songs tended to have sex differences in overall brain size. This pattern became stronger when we controlled statistically for female song complexity by using sex differences in song complexity. In species with large differences in song complexity, females evolved smaller brains than did males. Our results suggest no role for the evolution of extended neural space, as reflected by total brain size, owing to song complexity. However, factors associated with sexual selection mirrored by sex differences in song complexity were related to sexual dimorphism in overall brain size

Sex differences in the brain: implications for explaining autism

‘Empathizing’ is the capacity to predict and to respond to the behavior of agents (usually people) by inferring their mental states and responding to these with an appropriate emotion. ‘Systemizing’ is the capacity to predict and to respond to the behavior of non-agentive, deterministic systems, by analyzing input-operation-output relations and inferring the rules that govern such systems. At a population level, females are stronger empathizers and males stronger systemizers. The ‘extreme male brain’ theory posits that autism represents an extreme of the male pattern (impaired empathizing and enhanced systemizing). Here we suggest that specific aspects of autistic neuropathology may also be extremes of typical male neuroanatomy

Transcriptional and translational differences of microglia from male and female brains

Sex differences in brain structure and function are of substantial scientific interest because of sex-related susceptibility to psychiatric and neurological disorders. Neuroinflammation is a common denominator of many of these diseases and thus microglia as the brain ́s immunocompetent cells has come into focus in sex specific studies. Here we show differences in structure, function, transcriptomic and proteomic profile in microglia freshly isolated from male and female mouse brains. We show that male microglia are more frequent in specific brain areas, have a higher antigen presenting capacity, and appear to have a higher potential to respond to stimuli such as ATP reflected in higher baseline outward and inward currents and higher protein expression of purinergic receptors. Altogether, we provide a comprehensive resource to generate and validate hypotheses regarding brain sex differences that may support anticipated gender-based therapeutic strategies in the future.Aufgrund von geschlechtsspezifischen Ausprägungen von psychiatrischen und neurologischen Erkrankungen ist es von großer Wichtigkeit Unterschiede zwischen weiblichen und männlichen Gehirnstrukturen und ihren Funktionen zu untersuchen. Entzündungen im zentralen Nervensystem sind der gemeinsame Nenner von vielen dieser Krankheiten. Mikroglia als die immunkompetenten Zellen des Gehirns sind daher in den Fokus von geschlechtsspezifischen Studien gerückt. In meiner Arbeit zeige ich Unterschiede in Struktur und Funktion und im Transkriptom und Proteom Profil von Mikroglia aus frisch isolierten männlichen und weiblichen Mausgehirnen. Ich zeige, dass männliche Mikroglia in bestimmten Hirnregionen eine höhere Dichte aufweisen, eine größere Kapazität besitzen Antigene zu präsentieren und ein höheres Potential zeigen, auf Stimuli wie zum Beispiel ATP zu reagieren. Dies wird durch stärkere Auswärts- und Einwärtsströme über die Zellmembran unter normal Bedingungen und einer höheren Expression von purinergen Rezeptoren reflektiert. Ich stelle in dieser Arbeit umfangreiche Ressourcen bereit, um Hypothesen zu generieren und zu validieren, die sich mit Unterschieden zwischen weiblichen und männlichen Gehirnen und insbesondere Mikroglia befassen. Dies könnte für mögliche zukünftige geschlechtsbasierte therapeutische Ansätze eine unschätzbare Hilfe sein

Why Are Autism Spectrum Conditions More Prevalent in Males?

Autism Spectrum Conditions (ASC) are much more common in males, a bias that may offer clues to the etiology of this condition. Although the cause of this bias remains a mystery, we argue that it occurs because ASC is an extreme manifestation of the male brain. The extreme male brain (EMB) theory, first proposed in 1997, is an extension of the Empathizing-Systemizing (E-S) theory of typical sex differences that proposes that females on average have a stronger drive to empathize while males on average have a stronger drive to systemize. In this first major update since 2005, we describe some of the evidence relating to the EMB theory of ASC and consider how typical sex differences in brain structure may be relevant to ASC. One possible biological mechanism to account for the male bias is the effect of fetal testosterone (fT). We also consider alternative biological theories, the X and Y chromosome theories, and the reduced autosomal penetrance theory. None of these theories has yet been fully confirmed or refuted, though the weight of evidence in favor of the fT theory is growing from converging sources (longitudinal amniocentesis studies from pregnancy to age 10 years old, current hormone studies, and genetic association studies of SNPs in the sex steroid pathways). Ultimately, as these theories are not mutually exclusive and ASC is multi-factorial, they may help explain the male prevalence of ASC.</p

Sex-related differences in death control of somatic cells

In 2001, The United States Institute of Medicine (IOM) Committee on Understanding the Biology of Sex and Gender Differences concluded that ‘Sex…should be considered when designing and analysing studies in all areas and at all levels of biomedical and health-related research…’ and stated an apparent paradox i.e.: ‘every cell has a sex’ 1. Sex is defined as ‘the classification of living things, generally as male or female according to their reproductive organs and functions assigned by chromosomal complement’ whereas gender is defined as ‘a person's self representation as male or female, or how that person is responded to by social institutions based on the individual's gender presentation. Gender is rooted in biology and shaped by environment and experience’ 1. It is unchallenged that there are health differences between males and females and that social and cultural factors could contribute to the observed differences. Anyway, the sex-dependent differences also have a biological base which sometimes has not been deeply investigated. Scientists studying health differences between male and female aim to both considering social/cultural environment and investigating biological/molecular mechanisms different between sexes. Some experimental studies have elucidated important differences in cell death control 2. A sex disparity, in fact, has been shown both in the propensity to apoptosis and in the activation of the autophagic pathway. In the context of cell fate control, hormones represent important regulators of both apoptosis and autophagy. In the cardiovascular system, for example, oestrogens inhibit cardiomyocyte apoptosis by decreasing reactive oxygen species production and increasing intracellular antioxidants 3. Oestrogens may also indirectly control autophagy as they up-regulate urocortin 4, a neuropeptide hormone able to inhibiting autophagy in cardiomyocytes. Conversely, increasing evidence suggests possible adverse effects of androgens on the vasculature showing that androgens, as opposed to oestrogens, may worsen vascular dysfunction in men, thus contributing to sex-based differences in cardiovascular diseases 5. However, it is currently emerging that some cell death programs are differentially controlled by sex-related hormone-independent cellular genetics. Differences in cell death sensitivity in male and female may then occur in the absence of an hormonal context. This is not an immediately obvious finding; Penaloza C et al., 6 have shown that the apoptosis amount differs between the sexes in isolated embryonic cells exposed to similar conditions and this happens at embryonal stages where there are no hormonal influences. Previous studies had reported a sexual dimorphism in embryonic neuronal signal transduction pathways and consequently differences in cell survival 7. Death pathways in XX and XY cells have been poorly investigated as most studies have been performed on established cells lines often irrespective of their male or female origin. Recently, using freshly isolated cells from male and female individuals gave important information on sex disparity in cell fate control. Such sex specificity has been in part clarified thanks to cell culture models where sex steroids can be removed from the media. Even sex-related differences in caspase activation have been found to be independent on hormone exposure. More in detail, cell death occurring in cortical neurons after ischaemia proceeds predominantly via an apoptosis-inducing factor-dependent pathway (a caspase-independent pathway) in male neurons while proceeds via a cytochrome C-dependent pathway (a process mediated by caspase activation) in female neurons 8. In this context, a sex-specific microRNA expression after ischaemia has been described in in vivo studies. In particular, it has been demonstrated that microRNA-23a, by binding the mRNA of the caspase inhibitor named XIAP, induces its translational repression in females, leading to enhanced caspase signalling in the ischaemic female brain. This effect has been shown to be independent of circulating oestrogen levels 9. Sex differences in ischaemic brain injury and cerebrovascular regulation have been observed in clinical and experimental studies and an important determinant of such differences is also represented by the integrity of endothelial cells. In fact, endothelial function is improved in women compared with men, contributing to female cellular higher resistance after ischaemic brain injury. Gupta NC et al. 10 showed that female cerebrovascular endothelial cells express lower level of soluble epoxide hydrolase and consequently have higher levels of vasoprotective epoxyeicosatrienoic acids as compared with male endothelial cells. This study therefore presents a novel additional mechanism underlying differences between male and female cells in apoptotic response after oxygen-glucose deprivation, contributing to explain higher resistance observed in females as compared with males. This study remarks again that differences between male and female cells do not necessarily depend on the hormonal context but may be inherent the cells. We believe that this apparently paradoxical concept has not been sufficiently highlighted in the scientific literature. The present ‘Letter to the Editor’ therefore aims at underlining such an important issue which deserves more attention and discussion in the researchers' community. A practical consequence of sex-dependent discrepancies in cell death control is that cellular response to any stimulus or treatment, in any physiological or pathological context, may well depend on the sex of the cell line used; journals guidelines should therefore require authors to state in any case the sex of the cell lines used in any in vitro study. In addition, at least to some extent, sex-matched or sex-unmatched cell controls may be necessary in many experimental settings. In conclusion, sex-related differences in cell death mechanism may have strong implications for experimental studies and sexual dimorphism dependent on chromosomal rather than hormonal differences have important implications for planning preclinical studies and clinical interventions

A comparison of Voxel compression mapping & longitudinal Voxel-Based morphometry

Clinical motivation: Serial brain imaging can reveal patterns of change over time with important clinical implications for neurodegenerative disease [1]. We investigate the performance of four analysis methods, in terms of a comparison of 20 patients with probable AD to 20 age- and sex-matched controls, characterising differences in change from baseline to later scans

Sex Commonalities and Differences in Obesity-Related Alterations in Intrinsic Brain Activity and Connectivity.

OBJECTIVE:This study aimed to characterize obesity-related sex differences in the intrinsic activity and connectivity of the brain's reward networks. METHODS:Eighty-six women (n = 43) and men (n = 43) completed a 10-minute resting functional magnetic resonance imaging scan. Sex differences and commonalities in BMI-related frequency power distribution and reward seed-based connectivity were investigated by using partial least squares analysis. RESULTS:For whole-brain activity in both men and women, increased BMI was associated with increased slow-5 activity in the left globus pallidus (GP) and substantia nigra. In women only, increased BMI was associated with increased slow-4 activity in the right GP and bilateral putamen. For seed-based connectivity in women, increased BMI was associated with reduced slow-5 connectivity between the left GP and putamen and the emotion and cortical regulation regions, but in men, increased BMI was associated with increased connectivity with the medial frontal cortex. In both men and women, increased BMI was associated with increased slow-4 connectivity between the right GP and bilateral putamen and the emotion regulation and sensorimotor-related regions. CONCLUSIONS:The stronger relationship between increased BMI and decreased connectivity of core reward network components with cortical and emotion regulation regions in women may be related to the greater prevalence of emotional eating. The present findings suggest the importance of personalized treatments for obesity that consider the sex of the affected individual

What Is Safe Sex ? Understanding the Need for Sex Education Reform

Currently, the United States has no standardized requirement for sex education. This has precipitated a large gap in knowledge about safe sex and a lack of consensus in current social and educational policy. Debates about abstinence-only and comprehensive sex education have reached a standstill. In an effort to advance the discussion, this paper reveals that the neuroscience behind adolescent sexual risk taking provides underutilized evidence for comprehensive sex education programs. Research shows that adolescents have biological differences in their brain structure that result in a decision-making process different from that of adults, one that can preference rash decisions and potentially unsafe behavior. Therefore, current approaches to social and education policy for teens should change, to reflect this research and in-school curricula should evolve to more effectively reduce rates of unsafe sexual behaviors. Funding for such programs would more than pay for themselves with the resulting decrease in teen pregnancy and sexually transmitted diseases

Sex differences in the influence of body mass index on anatomical architecture of brain networks.

Background/objectivesThe brain has a central role in regulating ingestive behavior in obesity. Analogous to addiction behaviors, an imbalance in the processing of rewarding and salient stimuli results in maladaptive eating behaviors that override homeostatic needs. We performed network analysis based on graph theory to examine the association between body mass index (BMI) and network measures of integrity, information flow and global communication (centrality) in reward, salience and sensorimotor regions and to identify sex-related differences in these parameters.Subjects/methodsStructural and diffusion tensor imaging were obtained in a sample of 124 individuals (61 males and 63 females). Graph theory was applied to calculate anatomical network properties (centrality) for regions of the reward, salience and sensorimotor networks. General linear models with linear contrasts were performed to test for BMI and sex-related differences in measures of centrality, while controlling for age.ResultsIn both males and females, individuals with high BMI (obese and overweight) had greater anatomical centrality (greater connectivity) of reward (putamen) and salience (anterior insula) network regions. Sex differences were observed both in individuals with normal and elevated BMI. In individuals with high BMI, females compared to males showed greater centrality in reward (amygdala, hippocampus and nucleus accumbens) and salience (anterior mid-cingulate cortex) regions, while males compared to females had greater centrality in reward (putamen) and sensorimotor (posterior insula) regions.ConclusionsIn individuals with increased BMI, reward, salience and sensorimotor network regions are susceptible to topological restructuring in a sex-related manner. These findings highlight the influence of these regions on integrative processing of food-related stimuli and increased ingestive behavior in obesity, or in the influence of hedonic ingestion on brain topological restructuring. The observed sex differences emphasize the importance of considering sex differences in obesity pathophysiology