scholarly journals Sex differences in hippocampal cytokines after systemic immune challenge

2018 ◽  
Author(s):  
Ian C. Speirs ◽  
Natalie C. Tronson
Keyword(s):  
Sex Differences ◽  
Neural Function ◽  
Immune Challenge ◽  
Systemic Injection ◽  
Gm Csf ◽  
Cytokine Activation ◽  
Inflammatory State ◽  
Males And Females ◽  
Cytokine Networks ◽  
The Brain

ABSTRACTIllness or injury causes an inflammatory state consisting of activation of immune cells and increased production of cytokines in the periphery and in the brain, resulting changes in physiological processes, behavior, and cognition. The immune and neuroimmune response consist of a tightly controlled activation and resolution of cytokine networks, the precise patterns of which are determined, in part, by the immune stimulus. Importantly, the pattern of cytokines, rather than the presence of any individual cytokine, determines the functional outcome of immune signaling. In this project, we hypothesized that given sex differences in behavioral responses to immune challenge, the patterns of cytokine activation induced in the hippocampus after a systemic immune challenge differ between males and females. We examined 32 cytokines in the hippocampus and periphery of male and female mice 2, 6, 24, 48, and 168 hours after an acute systemic injection of lipopolysaccharides (LPS; 250μg/kg). All animals showed resolution of the neuroimmune response 168 hours after immune challenge Males and females differed in the specific cytokines activated in the hippocampus, the magnitude of elevation, and the timecourse of activation and resolution of neuroimmune signaling. Briefly, male-specific elevations included IFNγ, CSF1 (M-CSF) and CSF2 (GM-CSF), and the regulatory cytokine IL-10, whereas female-specific activation included the IL-2 family and the regulatory IL-4. Females showed rapid elevation and resolution of the hippocampal immune response, with cytokine levels peaking at 2 and 6 hours after immune challenge. In contrast, males showed slower and more persistent activation, with peaks at 6-24 hours. These findings demonstrate that sex differences in neuroimmune response are not limited to the intensity of the cytokine response, but more importantly differs in the cytokine networks activated. These findings suggest that delineating the broad, sex-specific patterns of cytokine activity in the brain is critical for understanding of the role of neuroimmune signaling in neural function.

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 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 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 Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain

2021 ◽  
Author(s):  
Carla Sanchis-Segura ◽  
Naiara Aguirre ◽  
Álvaro Javier Cruz-Gómez ◽  
Sonia Félix ◽  
Cristina Forn
Keyword(s):  
Sex Differences ◽  
Gray Matter Volume ◽  
Group Differences ◽  
Intracranial Volume ◽  
Brain Areas ◽  
High Classification Accuracy ◽  
Detailed Assessment ◽  
Functional Features ◽  
Males And Females ◽  
The Brain

Abstract Previous studies have shown that machine-learning (ML) algorithms can “predict” sex based on brain anatomical/ functional features. The high classification accuracy achieved by ML algorithms is often interpreted as revealing large differences between the brains of males and females and as confirming the existence of “male/female brains”. However, classification and estimation are quite different concepts, and using classification metrics as surrogate estimates of between-group differences results in major statistical and interpretative distortions. The present study illustrates these distortions and provides a novel and detailed assessment of multivariate sex differences in gray matter volume (GMVOL) that does not rely on classification metrics. Moreover, modeling and clustering techniques and analyses of similarities (ANOSIM) were used to identify the brain areas that contribute the most to these multivariate differences, and to empirically assess whether they assemble into two sex-typical profiles. Results revealed that multivariate sex differences in GMVOL: 1) are “large” if not adjusted for total intracranial volume (TIV) variation, but “small” when controlling for this variable; 2) differ in size between individuals and also depends on the ML algorithm used for their calculation 3) do not stem from two sex-typical profiles, and so describing them in terms of “male/female brains” is misleading.

scholarly journals Enduring and sex-specific changes in hippocampal gene expression after a subchronic immune challenge

2019 ◽  
Author(s):  
Daria Tchessalova ◽  
Natalie C. Tronson
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Transcriptional Response ◽  
Neural Function ◽  
Immune Challenge ◽  
Memory Decline ◽  
Memory Impairments ◽  
Differential Gene ◽  
The Brain ◽  
Neuroimmune Activation

AbstractMajor illnesses, including heart attack and sepsis, can cause cognitive impairments, depression, and progressive memory decline that persist long after recovery from the original illness. In rodent models of sepsis or subchronic immune challenge, memory deficits also persist for weeks or months, even in the absence of ongoing neuroimmune activation. This raises the question of what mechanisms in the brain mediate such persistent changes in neural function. Here, we used RNA-sequencing as a large-scale, unbiased approach to identify changes in hippocampal gene expression long after a subchronic immune challenge previously established to cause persistent memory impairments in both males and females. We observed enduring dysregulation of gene expression three months after the end of a subchronic immune challenge, Surprisingly, we also found striking sex differences in both the magnitude of changes and the specific genes and pathways altered, where males showed persistent changes in both immune- and plasticity-related genes three months after immune challenge, whereas females showed few such changes. In contrast, females showed striking differential gene expression in response to a subsequent immune challenge. Thus, immune activation has enduring and sex-specific consequences for hippocampal gene expression and the transcriptional response to subsequent stimuli. Together with findings of long-lasting memory impairments after immune challenge, these data suggest that illnesses can cause enduring vulnerability to, cognitive decline, affective disorders, and memory impairments via dysregulation of transcriptional processes in the brain.

scholarly journals Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain

2022 ◽  
Author(s):  
Carla Sanchis-Segura ◽  
Naiara Aguirre ◽  
Álvaro Javier Cruz-Gómez ◽  
Sonia Félix ◽  
Cristina Forn
Keyword(s):  
Sex Differences ◽  
Gray Matter Volume ◽  
Group Differences ◽  
Intracranial Volume ◽  
Brain Areas ◽  
High Classification Accuracy ◽  
Detailed Assessment ◽  
Functional Features ◽  
Males And Females ◽  
The Brain

Abstract Previous studies have shown that machine-learning (ML) algorithms can “predict” sex based on brain anatomical/ functional features. The high classification accuracy achieved by ML algorithms is often interpreted as revealing large differences between the brains of males and females and as confirming the existence of “male/female brains”. However, classification and estimation are quite different concepts, and using classification metrics as surrogate estimates of between-group differences results in major statistical and interpretative distortions. The present study illustrates these distortions and provides a novel and detailed assessment of multivariate sex differences in gray matter volume (GMVOL) that does not rely on classification metrics. Moreover, modeling and clustering techniques and analyses of similarities (ANOSIM) were used to identify the brain areas that contribute the most to these multivariate differences, and to empirically assess whether they assemble into two sex-typical profiles. Results revealed that multivariate sex differences in GMVOL: 1) are “large” if not adjusted for total intracranial volume (TIV) variation, but “small” when controlling for this variable; 2) differ in size between individuals and also depends on the ML algorithm used for their calculation 3) do not stem from two sex-typical profiles, and so describing them in terms of “male/female brains” is misleading.

scholarly journals Establishing a link between sex-related differences in the structural connectome and behaviour

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150111 ◽  
Author(s):  
Birkan Tunç ◽  
Berkan Solmaz ◽  
Drew Parker ◽  
Theodore D. Satterthwaite ◽  
Mark A. Elliott ◽  
...  
Keyword(s):  
Sex Differences ◽  
Brain Structure ◽  
Research Effort ◽  
Structural Connectivity ◽  
Human Mind ◽  
Brain Network ◽  
Attention And Memory ◽  
Behavioural Patterns ◽  
Males And Females ◽  
The Brain

Recent years have witnessed an increased attention to studies of sex differences, partly because such differences offer important considerations for personalized medicine. While the presence of sex differences in human behaviour is well documented, our knowledge of their anatomical foundations in the brain is still relatively limited. As a natural gateway to fathom the human mind and behaviour, studies concentrating on the human brain network constitute an important segment of the research effort to investigate sex differences. Using a large sample of healthy young individuals, each assessed with diffusion MRI and a computerized neurocognitive battery, we conducted a comprehensive set of experiments examining sex-related differences in the meso-scale structures of the human connectome and elucidated how these differences may relate to sex differences at the level of behaviour. Our results suggest that behavioural sex differences, which indicate complementarity of males and females, are accompanied by related differences in brain structure across development. When using subnetworks that are defined over functional and behavioural domains, we observed increased structural connectivity related to the motor, sensory and executive function subnetworks in males. In females, subnetworks associated with social motivation, attention and memory tasks had higher connectivity. Males showed higher modularity compared to females, with females having higher inter-modular connectivity. Applying multivariate analysis, we showed an increasing separation between males and females in the course of development, not only in behavioural patterns but also in brain structure. We also showed that these behavioural and structural patterns correlate with each other, establishing a reliable link between brain and behaviour.

Sex Differences in Immune Gene Expression in the Brain of a Small Shorebird

2021 ◽  
Author(s):  
José O. Valdebenito ◽  
Kathryn H. Maher ◽  
Gergely Zachar ◽  
Qin Huang ◽  
Zhengwang Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Immune Function ◽  
Life Histories ◽  
Laboratory Animals ◽  
Evolutionary Significance ◽  
Immune Gene ◽  
Immune Gene Expression ◽  
Males And Females ◽  
The Brain

Abstract Background: Males and females often exhibit different behaviour, life histories and ecology, and sex differences are typically reflected in their brains. Neuronal protection and maintenance include complex processes led by the microglia that also interact with metabolites such as hormones or immune components. Despite increasing interest in sex-specific brain activation in laboratory animals, the crucial significance of immune function protecting in the brain of wildlife is widely lacking. Here, we study sex-specific expression of immune genes in the brain of a small shorebird, the Kentish plover (Charadrius alexandrinus), that is an emerging model of mating system evolution and speciation. We compare immune gene expression patterns between adult males and adult females in two wild breeding populations in contrasting habitats: a coastal sea-level population and a high-altitude inland population in China.Results: Our analysis yielded 379 genes associated with immune function. We show a significant male-biased immune gene upregulation, which is in line with ecological studies that showed higher survival in males than in females. Immune gene expression in the brain did not differ in upregulation between the coastal and inland populations.Conclusions: We discuss the role of dosage compensation in our findings and their evolutionary significance mediated by sex-specific survival and neuronal deterioration. Similar expression profiles in the coastal and inland populations suggest comparable pathogen pressures between the habitats. We call for further studies on gene expressions of males and females in wild population to understand the implications of immune function for life-histories and demography in natural systems.

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.

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