Signatures of sex: Sex differences in gene expression in the vertebrate brain

Gegenhuber, Bruno; Tollkühn, Jessica

doi:10.1002/wdev.348

Cited by 57 publications

(56 citation statements)

References 263 publications

(324 reference statements)

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“…The BNST expresses both androgen and estrogen receptors (Bamshad et al, 1993;Gegenhuber and Tollkuhn, 2019;Juntti et al, 2010), yet sex differences in the behavioral effects of losing encounters are not affected by gonadectomy in adult males or females (Trainor et al, 2013). However, since losing aggressive encounters leads to the expression of social vigilance in prepubertal males and females (Wright and Trainor in preparation), this suggests that gonadal hormones such as T may reprogram the BNST during adolescence.…”

Section: Bed Nucleus Of the Stria Terminalis (Bnst)mentioning

confidence: 99%

The challenge hypothesis revisited: Focus on reproductive experience and neural mechanisms

Marler

Trainor

2020

Hormones and Behavior

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Our review focuses on findings from mammals as part of a Special Issue "30th Anniversary of the Challenge Hypothesis". Here we put forth an integration of the mechanisms through which testosterone controls territorial behavior and consider how reproductive experience may alter these mechanisms. The emphasis is placed on the function of socially induced increases in testosterone (T) pulses, which occur in response to social interactions, as elegantly developed by Wingfield and colleagues. We focus on findings from the monogamous California mouse, as data from this species shows that reproductive status is a key factor influencing social interactions, site fidelity, and vigilance for offspring defense. Specifically, we examine differences in T pulses in sexually naïve versus sexually experienced pair bonded males. Testosterone pulses influence processes such as social decision making, the winner-challenge effect, and location preferences through rewarding effects of T. We also consider how social and predatory vigilance contribute to T pulses and how these interactions contribute to a territory centered around maximizing reproduction. Possible underlying mechanisms for these effects include the nucleus accumbens (rewarding effects of testosterone), hippocampus (spatial memories for territories), and the bed nucleus of the stria terminalis (social vigilance). The development of the challenge effect has provided an ideal framework for understanding the complex network of behavioral, environmental, physiological and neural mechanisms that ultimately relates to competition and territoriality across taxa. The opportunity to merge research on the challenge effect using both laboratory and field research to understand social behavior is unparalleled.

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Section: Bed Nucleus Of the Stria Terminalis (Bnst)mentioning

confidence: 99%

The challenge hypothesis revisited: Focus on reproductive experience and neural mechanisms

Marler

Trainor

2020

Hormones and Behavior

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“…15,16 Similarly, other regions, such as the hippocampus and the amygdala, have higher activation for women in response to negative emotions. 17,18 Many of these regions also show sex dimorphism in structure, [19][20][21][22][23][24][25][26][27] connectivity, 28 cell composition, 29,30 and transcriptional profile [31][32][33][34][35][36] (Figure 1).…”

mentioning

confidence: 99%

Sex differences: Transcriptional signatures of stress exposure in male and female brains

Brivio

López

Chen

2020

Genes Brain and Behavior

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More than two‐thirds of patients suffering from stress‐related disorders are women but over two‐thirds of suicide completers are men. These are just some examples of the many sex differences in the prevalence and manifestations of stress‐related disorders, such as major depressive disorder, post‐traumatic stress disorder, and anxiety disorders, which have been extensively documented in clinical research. Nonetheless, the molecular origins of this sex dimorphism are still quite obscure. In response to this lack of knowledge, the NIH recently advocated implementing sex as biological variable in the design of preclinical studies across disciplines. As a result, a newly emerging field within psychiatry is trying to elucidate the molecular causes underlying the clinically described sex dimorphism. Several studies in rodents and humans have already identified many stress‐related genes that are regulated by acute and chronic stress in a sex‐specific fashion. Furthermore, current transcriptomic studies have shown that pathways and networks in male and female individuals are not equally affected by stress exposure. In this review, we give an overview of transcriptional studies designed to understand how sex influences stress‐specific transcriptomic changes in rodent models, as well as human psychiatric patients, highlighting the use of different methodological techniques. Understanding which mechanisms are more affected in males, and which in females, may lead to the identification of sex‐specific mechanisms, their selective contribution to stress susceptibility, and their role in the development of stress‐related psychiatric disorders.

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“…Knowledge of BNST structure and function during adolescent development is sparse. Several subregions of the BNST are larger in males compared with females (Allen & Gorski, 1990;Campi, Jameson, & Trainor, 2013;Morishita, Maejima, & Tsukahara, 2017), and some show sex differences in chemoarchitecture (Bamshad, Novak, & Devries, 1993;Gegenhuber & Tollkuhn, 2019;Juntti et al, 2010). These sex differences in the neuroanatomy likely contribute to sex-dependent reproductive behaviors (Juntti et al, 2010) and learning patterns (Bangasser, Santollo, & Shors, 2005;Bangasser & Shors, 2008).…”

Section: Duquementioning

confidence: 99%

Anxious to see you: Neuroendocrine mechanisms of social vigilance and anxiety during adolescence

Wright

Hostinar

Trainor

2019

Eur J of Neuroscience

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Social vigilance is a behavioral strategy commonly used in adverse or changing social environments. In animals, a combination of avoidance and vigilance allows an individual to evade potentially dangerous confrontations while monitoring the social environment to identify favorable changes. However, prolonged use of this behavioral strategy in humans is associated with increased risk of anxiety disorders, a major burden for human health. Elucidating the mechanisms of social vigilance in animals could provide important clues for new treatment strategies for social anxiety. Importantly, during adolescence the prevalence of social anxiety increases significantly. We hypothesize that many of the actions typically characterized as anxiety behaviors begin to emerge during this time as strategies for navigating more complex social structures. Here, we consider how the social environment and the pubertal transition shape neural circuits that modulate social vigilance, focusing on the bed nucleus of the stria terminalis and prefrontal cortex. The emergence of gonadal hormone secretion during adolescence has important effects on the function and structure of these circuits, and may play a role in the emergence of a notable sex difference in anxiety rates across adolescence. However, the significance of these changes in the context of anxiety is still uncertain, as not enough studies are sufficiently powered to evaluate sex as a biological variable. We conclude that greater integration between human and animal models will aid the development of more effective strategies for treating social anxiety.

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Signatures of sex: Sex differences in gene expression in the vertebrate brain

Cited by 57 publications

References 263 publications

The challenge hypothesis revisited: Focus on reproductive experience and neural mechanisms

The challenge hypothesis revisited: Focus on reproductive experience and neural mechanisms

Sex differences: Transcriptional signatures of stress exposure in male and female brains

Anxious to see you: Neuroendocrine mechanisms of social vigilance and anxiety during adolescence

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