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

2016 ◽  
Vol 18 (4) ◽  
pp. 361-372 ◽  

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.

2016 ◽  
Vol 18 (4) ◽  
pp. 373-383 ◽  

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.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Joseph M. Baker ◽  
Ning Liu ◽  
Xu Cui ◽  
Pascal Vrticka ◽  
Manish Saggar ◽  
...  

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.


2016 ◽  
Vol 371 (1688) ◽  
pp. 20150106 ◽  
Author(s):  
Margaret M. McCarthy

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.


2016 ◽  
Vol 371 (1688) ◽  
pp. 20150117 ◽  
Author(s):  
Gregory F. Ball

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.


2020 ◽  
Vol 6 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Yosef Avchalumov ◽  
Chitra D. Mandyam

Alcohol is one of the oldest pharmacological agents used for its sedative/hypnotic effects, and alcohol abuse and alcohol use disorder (AUD) continues to be major public health issue. AUD is strongly indicated to be a brain disorder, and the molecular and cellular mechanism/s by which alcohol produces its effects in the brain are only now beginning to be understood. In the brain, synaptic plasticity or strengthening or weakening of synapses, can be enhanced or reduced by a variety of stimulation paradigms. Synaptic plasticity is thought to be responsible for important processes involved in the cellular mechanisms of learning and memory. Long-term potentiation (LTP) is a form of synaptic plasticity, and occurs via N-methyl-D-aspartate type glutamate receptor (NMDAR or GluN) dependent and independent mechanisms. In particular, NMDARs are a major target of alcohol, and are implicated in different types of learning and memory. Therefore, understanding the effect of alcohol on synaptic plasticity and transmission mediated by glutamatergic signaling is becoming important, and this will help us understand the significant contribution of the glutamatergic system in AUD. In the first part of this review, we will briefly discuss the mechanisms underlying long term synaptic plasticity in the dorsal striatum, neocortex and the hippocampus. In the second part we will discuss how alcohol (ethanol, EtOH) can modulate long term synaptic plasticity in these three brain regions, mainly from neurophysiological and electrophysiological studies. Taken together, understanding the mechanism(s) underlying alcohol induced changes in brain function may lead to the development of more effective therapeutic agents to reduce AUDs.


1985 ◽  
Vol 5 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Alison M. Crane ◽  
Louis Sokoloff

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260577
Author(s):  
Alyssa Bernanke ◽  
Elizabeth Burnette ◽  
Justine Murphy ◽  
Nathaniel Hernandez ◽  
Sara Zimmerman ◽  
...  

Females are more affected by psychiatric illnesses including eating disorders, depression, and post-traumatic stress disorder than males. However, the neural mechanisms mediating these sex differences are poorly understood. Animal models can be useful in exploring such neural mechanisms. Conditioned taste aversion (CTA) is a behavioral task that assesses how animals process the competition between associated reinforcing and aversive stimuli in subsequent task performance, a process critical to healthy behavior in many domains. The purpose of the present study was to identify sex differences in this behavior and associated neural responses. We hypothesized that females would value the rewarding stimulus (Boost®) relative to the aversive stimulus (LiCl) more than males in performing CTA. We evaluated behavior (Boost® intake, LiCl-induced behaviors, ultrasonic vocalizations (USVs), CTA performance) and Fos activation in relevant brain regions after the acute stimuli [acute Boost® (AB), acute LiCl (AL)] and the context-only task control (COT), Boost® only task (BOT) and Boost®-LiCl task (BLT). Acutely, females drank more Boost® than males but showed similar aversive behaviors after LiCl. Females and males performed CTA similarly. Both sexes produced 55 kHz USVs anticipating BOT and inhibited these calls in the BLT. However, more females emitted both 22 kHz and 55 kHz USVs in the BLT than males: the latter correlated with less CTA. Estrous cycle stage also influenced 55 kHz USVs. Fos responses were similar in males and females after AB or AL. Females engaged the gustatory cortex and ventral tegmental area (VTA) more than males during the BOT and males engaged the amygdala more than females in both the BOT and BLT. Network analysis of correlated Fos responses across brain regions identified two unique networks characterizing the BOT and BLT, in both of which the VTA played a central role. In situ hybridization with RNAscope identified a population of D1-receptor expressing cells in the CeA that responded to Boost® and D2 receptor-expressing cells that responded to LiCl. The present study suggests that males and females differentially process the affective valence of a stimulus to produce the same goal-directed behavior.


2021 ◽  
pp. 81-108
Author(s):  
Susan D. Healy

Morphological and behavioural differences between the sexes are ubiquitous across the animal kingdom. There is also good evidence for differences in some brain regions between males and females, in humans, some rodents, and many songbirds. I look at the data for sex differences in cognition, of which there are some that show differences in spatial cognition and in hippocampal structure, at least some of which may be explained by variation in hormone levels. The thesis of The Mating Mind by Geoffrey Miller considerably increased interest in using sexual selection to explain variation in brain size. From female mate choice, male–male competition, sperm competition, mating strategy, to parental care, there are some data that appear to support selection acting on one species rather than the other in sexually a selected manner but I conclude that the data are not generally supportive of the Sexual Brain Hypothesis.


1999 ◽  
Vol 23 (1) ◽  
pp. 13-22 ◽  
Author(s):  
XJ Pi ◽  
DR Grattan

This study investigated expression of prolactin receptor (PRL-R) mRNA in selected hypothalamic nuclei of lactating rats (days 7-10 post partum) compared with dioestrous rats. Rat brains were frozen with liquid nitrogen and cut into coronal sections of 300 microm. From these sections, tissues were micropunched from the parietal cortex (CTX), choroid plexus (ChP), and five hypothalamic regions: supraoptic (SO), paraventricular (Pa), arcuate (Arc) and ventromedial hypothalamic (VMH) nuclei, and median eminence (ME). Expression of both short and long forms of PRL-R mRNA were evaluated by reverse transcription-PCR and Southern hybridisation. The results showed that the relative amount of short form mRNA in the ChP of lactating rats was significantly higher than in dioestrous rats. The short form of PRL-R mRNA was undetectable in the SO, Pa, VMH of dioestrous rats but was expressed at a significant level in lactating rats. Levels of long form mRNA in the ChP, SO, Pa and VMH in lactating rats were significantly increased compared with dioestrous rats. Moreover, the long form mRNA was induced in the CTX of lactating rats. In the Arc, levels of both forms of PRL-R mRNA tended to increase in lactating rats compared with dioestrous rats but changes were not statistically significant. Neither form of PRL-R mRNA was detectable in the ME in the two animal models. Increased expression of PRL-R mRNA in specific brain regions during lactation is consistent with the variety of PRL effects on the brain, and may help to explain profound physiological changes in the lactating mother.


2021 ◽  
Author(s):  
Carla Sanchis-Segura ◽  
Naiara Aguirre ◽  
Álvaro Javier Cruz-Gómez ◽  
Sonia Félix ◽  
Cristina Forn

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.


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