scholarly journals Sex in the brain: hormones and sex differences

2016 ◽  
Vol 18 (4) ◽  
pp. 373-383 ◽  
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Genetic Factors ◽  
Motor Coordination ◽  
Brain Regions ◽  
New Era ◽  
Brain Functions ◽  
Opioid Sensitivity ◽  
Males And Females ◽  
The Brain

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

scholarly journals Sex differences in the developing brain as a source of inherent risk

2016 ◽  
Vol 18 (4) ◽  
pp. 361-372 ◽  
Keyword(s):  
Sex Differences ◽  
Brain Regions ◽  
Impact Behavior ◽  
Physiological Changes ◽  
Cellular Mechanisms ◽  
Multiple Factors ◽  
Inherent Risk ◽  
Males And Females ◽  
Unifying Principles ◽  
The Brain

Brain development diverges in males and females in response to androgen production by the fetal testis. This sexual differentiation of the brain occurs during a sensitive window and induces enduring neuroanatomical and physiological changes that profoundly impact behavior. What we know about the contribution of sex chromosomes is still emerging, highlighting the need to integrate multiple factors into understanding sex differences, including the importance of context. The cellular mechanisms are best modeled in rodents and have provided both unifying principles and surprising specifics. Markedly distinct signaling pathways direct differentiation in specific brain regions, resulting in mosaicism of relative maleness, femaleness, and sameness through-out the brain, while canalization both exaggerates and constrains sex differences. Non-neuronal cells and inflammatory mediators are found in greater number and at higher levels in parts of male brains. This higher baseline of inflammation is speculated to increase male vulnerability to developmental neuropsychiatric disorders that are triggered by inflammation.

scholarly journals OP0013 SEX DIFFERENCES IN AUTOIMMUNE DISEASE SUSCEPTIBILITY; A MULTI-OMIC APPROACH

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 8.1-8
Author(s):  
G. Robinson ◽  
K. Waddington ◽  
J. Peng ◽  
A. Radziszewska ◽  
H. Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
Lipid Metabolism ◽  
Sex Hormones ◽  
Cell Function ◽  
Immune Cell ◽  
Density Lipoprotein ◽  
Hormone Treatment ◽  
Immune Cell Function ◽  
Immune Cell Subsets ◽  
Males And Females

Background:Males and females have altered immune responses resulting in variation in autoimmune and cardiovascular disease risk (CVR). Recently, these differences have played a role in the inflammatory response to COVID-19. Sex differences exist in the frequency and activity of immune-cell subsets but mechanisms underlying sexual dimorphism remain unknown. Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder that commonly emerges during puberty, has a strong female prevalence (female:male ratio, 4.5:1) and results in an increased CVR. JSLE is characterised by chronic inflammation and dyslipidaemia, where cardiovascular disease is a leading cause of mortality for patients. Our previous work identified a link between immune cell function and lipid metabolism in adult-onset SLE. We hypothesised that sex hormones could influence both lipid metabolism and immune cell function and this could determine sex-specific susceptibility to JSLE and associated CVR.Objectives:We investigated the role of sex hormones in modifying systemic lipid metabolism and inflammation.Methods:Nuclear magnetic resonance spectroscopy based serum metabolomics measuring over 130 lipoproteins (14-subsets with lipid compositions), flow cytometry measuring immune-cells, and RNA-sequencing were used to assess the metabolic and immune profile in young, pre/post-pubertal males (n=10/17) and females (n=10/23) and in individuals with gender-dysphoria (GD) under cross-hormone treatment (trans-male/female, n=26/25). This analysis was also performed on a cohort of post-pubertal male (n=12) and female (n=23) JSLE patients. Data was analysed by logistic regression, balanced random forest machine learning (BRF-ML), differential gene expression (DEG) and pathway analysis.Results:Post-pubertal males had significantly reduced cardio-protective high-density lipoprotein (HDL) subsets (p<0.0001) and increased cardio-pathogenic very-low-density lipoprotein subsets (p<0.0001) compared to females. These differences were not observed pre-puberty and were reversed significantly by cross-hormone treatment in GD individuals, suggesting that sex hormones regulate lipid metabolism in-vivo.BRF-ML (28 immune-cell subsets) identified an increased frequency of anti-inflammatory regulatory T-cells (Tregs) in post-pubertal males compared to females (p=0.0097). These Tregs were also more suppressive in males compared to females. Differences in Treg frequency were seen pre-puberty and were not altered by sex hormone treatment in GD individuals. However, Treg DEGs and functional transcriptomic pathways altered between post-pubertal males and females, including those involved in inflammatory signalling, overlapped with those altered by hormones in GD, suggesting hormones may also drive Treg functional changes. In addition, HDL metabolites modified by hormones showed differential associations with Treg phenotypes between post-pubertal males and females.Strikingly, sex differences in lipoproteins and Tregs were lost in JSLE, suggesting hormone signalling could be dysregulated in the pathogenesis of autoimmunity and could increase CVR for patients.Conclusion:Sex hormones drive altered lipoprotein metabolism and functional transcriptomic pathways in Tregs. Males have a lipoprotein profile associated with increased CVR, but a more anti-inflammatory immune profile compared to females. Together, this could explain sex differences in inflammatory disease susceptibilities and inform future sex-specific therapeutic strategies for the management of both JSLE and CVR.Acknowledgements:Lupus UKRosetrees TrustVersus ArthritisNIHR UCLH Biomedical Research CentreDisclosure of Interests:None declared

scholarly journals Sex differences in neural and behavioral signatures of cooperation revealed by fNIRS hyperscanning

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Joseph M. Baker ◽  
Ning Liu ◽  
Xu Cui ◽  
Pascal Vrticka ◽  
Manish Saggar ◽  
...  
Keyword(s):  
Sex Differences ◽  
Temporal Cortex ◽  
Neural Correlates ◽  
Behavioral Signatures ◽  
Computer Based ◽  
Males And Females ◽  
Brain And Behavior ◽  
The Right ◽  
And Behavior ◽  
The Brain

Abstract Researchers from multiple fields have sought to understand how sex moderates human social behavior. While over 50 years of research has revealed differences in cooperation behavior of males and females, the underlying neural correlates of these sex differences have not been explained. A missing and fundamental element of this puzzle is an understanding of how the sex composition of an interacting dyad influences the brain and behavior during cooperation. Using fNIRS-based hyperscanning in 111 same- and mixed-sex dyads, we identified significant behavioral and neural sex-related differences in association with a computer-based cooperation task. Dyads containing at least one male demonstrated significantly higher behavioral performance than female/female dyads. Individual males and females showed significant activation in the right frontopolar and right inferior prefrontal cortices, although this activation was greater in females compared to males. Female/female dyad’s exhibited significant inter-brain coherence within the right temporal cortex, while significant coherence in male/male dyads occurred in the right inferior prefrontal cortex. Significant coherence was not observed in mixed-sex dyads. Finally, for same-sex dyads only, task-related inter-brain coherence was positively correlated with cooperation task performance. Our results highlight multiple important and previously undetected influences of sex on concurrent neural and behavioral signatures of cooperation.

scholarly journals Multifaceted origins of sex differences in the brain

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150106 ◽  
Author(s):  
Margaret M. McCarthy
Keyword(s):  
Sex Differences ◽  
State Of The Art ◽  
Human Subjects ◽  
Special Issue ◽  
Molecular Analyses ◽  
The Past ◽  
Current State ◽  
Biological Variable ◽  
Males And Females ◽  
The Brain

Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.

scholarly journals Species variation in the degree of sex differences in brain and behaviour related to birdsong: adaptations and constraints

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150117 ◽  
Author(s):  
Gregory F. Ball
Keyword(s):  
Sex Differences ◽  
Neural Circuit ◽  
Species Variation ◽  
Song System ◽  
System A ◽  
Song Control System ◽  
Males And Females ◽  
Song Control ◽  
Area X ◽  
The Brain

The song-control system, a neural circuit that controls the learning and production of birdsong, provided the first example in vertebrates of prominent macro-morphological sex differences in the brain. Forebrain nuclei HVC, robust nucleus of the arcopallium (RA) and area X all exhibit prominent male-biased sex differences in volume in zebra finches and canaries. Subsequent studies compared species that exhibited different degrees of a sex difference in song behaviour and revealed an overall positive correlation between male biases in song behaviour and male biases in the volume of the song nuclei. However, several exceptions have been described in which male biases in HVC and RA are observed even though song behaviour is equal or even female-biased. Other phenotypic measures exhibit lability in both sexes. In the duetting plain-tailed wren ( Pheugopedius euophrys ), males and females have auditory cells in the song system that are tuned to the joint song the two sexes produce rather than just male or female components. These findings suggest that there may be constraints on the adaptive response of the song system to ecological conditions as assessed by nucleus volume but that other critical variables regulating song can respond so that each sex can modify its song behaviour as needed.

scholarly journals Sex Differences and the Influence of Sex Hormones on Cognition through Adulthood and the Aging Process

2018 ◽  
Vol 8 (9) ◽  
pp. 163 ◽  
Author(s):  
Caroline Gurvich ◽  
Kate Hoy ◽  
Natalie Thomas ◽  
Jayashri Kulkarni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Functioning ◽  
Sex Hormones ◽  
Reproductive Function ◽  
Health And Disease ◽  
And Function ◽  
The Brain

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.

scholarly journals STAB: a spatio-temporal cell atlas of the human brain

2020 ◽  
Vol 49 (D1) ◽  
pp. D1029-D1037
Author(s):  
Liting Song ◽  
Shaojun Pan ◽  
Zichao Zhang ◽  
Longhao Jia ◽  
Wei-Hua Chen ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Temporal Dynamics ◽  
Cell Types ◽  
Brain Regions ◽  
Molecular Characteristics ◽  
Great Effort ◽  
Brain Functions ◽  
Spatio Temporal ◽  
The Brain

Abstract The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.

Effective brain connectivity estimation between active brain regions in autism using the dual Kalman-based method

2020 ◽  
Vol 65 (1) ◽  
pp. 23-32
Author(s):  
Mehdi Rajabioun ◽  
Ali Motie Nasrabadi ◽  
Mohammad Bagher Shamsollahi ◽  
Robert Coben
Keyword(s):  
Resting State ◽  
Brain Connectivity ◽  
Effective Connectivity ◽  
Estimation Error ◽  
Brain Regions ◽  
Estimation Methods ◽  
Estimation Errors ◽  
Normal Children ◽  
Brain Functions ◽  
The Brain

AbstractBrain connectivity estimation is a useful method to study brain functions and diagnose neuroscience disorders. Effective connectivity is a subdivision of brain connectivity which discusses the causal relationship between different parts of the brain. In this study, a dual Kalman-based method is used for effective connectivity estimation. Because of connectivity changes in autism, the method is applied to autistic signals for effective connectivity estimation. For method validation, the dual Kalman based method is compared with other connectivity estimation methods by estimation error and the dual Kalman-based method gives acceptable results with less estimation errors. Then, connectivities between active brain regions of autistic and normal children in the resting state are estimated and compared. In this simulation, the brain is divided into eight regions and the connectivity between regions and within them is calculated. It can be concluded from the results that in the resting state condition the effective connectivity of active regions is decreased between regions and is increased within each region in autistic children. In another result, by averaging the connectivity between the extracted active sources of each region, the connectivity between the left and right of the central part is more than that in other regions and the connectivity in the occipital part is less than that in others.

scholarly journals Local Cerebral Glucose Utilization in Normal Female Rats: Variations during the Estrous Cycle and Comparison with Males

1985 ◽  
Vol 5 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Alison M. Crane ◽  
Louis Sokoloff
Keyword(s):  
Estrous Cycle ◽  
Glucose Utilization ◽  
Brain Regions ◽  
Female Rats ◽  
Male Rats ◽  
Normal Male ◽  
Normal Female ◽  
Female Rat ◽  
Males And Females ◽  
The Brain

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.

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