Recipe for a sexually dimorphic brain: Ingredients include ovarian and testicular hormones

1998 ◽  
Vol 21 (3) ◽  
pp. 330-331 ◽  
Author(s):  
Diane F. Halpern

New knowledge about the sexual differentiation of the brain profoundly changes our understanding of basic topics in brain development such as the false dichotomy between long-lasting and transient effects of hormones on neural activity, the importance of ovarian hormones in brain development, the plasticity of neural structures throughout the life span, and the way measurement issues affect research conclusions.

2021 ◽  
Vol 12 ◽  
Author(s):  
Austin Ferro ◽  
Yohan S. S. Auguste ◽  
Lucas Cheadle

Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.


Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3681-3691 ◽  
Author(s):  
Beverly S. Rubin ◽  
Jenny R. Lenkowski ◽  
Cheryl M. Schaeberle ◽  
Laura N. Vandenberg ◽  
Paul M. Ronsheim ◽  
...  

Humans are routinely exposed to bisphenol A (BPA), an estrogenic chemical present in food and beverage containers, dental composites, and many products in the home and workplace. BPA binds both classical nuclear estrogen receptors and facilitates membrane-initiated estrogenic effects. Here we explore the ability of environmentally relevant exposure to BPA to affect anatomical and functional measures of brain development and sexual differentiation. Anatomical evidence of alterations in brain sexual differentiation were examined in male and female offspring born to mouse dams exposed to 0, 25, or 250 ng BPA/kg body weight per day from the evening of d 8 of gestation through d 16 of lactation. These studies examined the sexually dimorphic population of tyrosine hydroxylase (TH) neurons in the rostral periventricular preoptic area, an important brain region for estrous cyclicity and estrogen-positive feedback. The significant sex differences in TH neuron number observed in control offspring were diminished or obliterated in offspring exposed to BPA primarily because of a decline in TH neuron number in BPA-exposed females. As a functional endpoint of BPA action on brain sexual differentiation, we examined the effects of perinatal BPA exposure on sexually dimorphic behaviors in the open field. Data from these studies revealed significant sex differences in the vehicle-exposed offspring that were not observed in the BPA-exposed offspring. These data indicate that BPA may be capable of altering important events during critical periods of brain development.


2016 ◽  
Vol 371 (1688) ◽  
pp. 20150122 ◽  
Author(s):  
Eldin Jašarević ◽  
Kathleen E. Morrison ◽  
Tracy L. Bale

In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals. Importantly, the composition and functional potential of the gut microbiome undergoes many transitions that parallel dynamic periods of brain development and maturation for which distinct sex differences have been identified. Here, we discuss the sexually dimorphic development, maturation and maintenance of the gut microbiome–brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan.


1998 ◽  
Vol 21 (3) ◽  
pp. 341-346
Author(s):  
Roslyn Holly Fitch ◽  
Victor H. Denenberg

A number of commentators agree that the evidence reviewed in the target article supports a previously unrecognized role for ovarian hormones in feminization of the brain. Others question this view, suggesting that the traditional model of sexual differentiation already accounts for ovarian influence. This position is supported by various reinterpretations of the data presented (e.g., ovarian effects are secondary to the presence/absence of androgen, ovarian effects are smaller than testicular effects, ovarian effects are not organizational). We discuss these issues, and reiterate our position that evidence of neurobehavioral ovarian effects is incompatible with the currently accepted model of sexual differentiation. Other points regarding species generalizations, the direct versus indirect action of estrogen, and nonhormonal mechanisms of sexual differentiation are also discussed. Finally, we address the controversial issue of using ratio scores in the assessment of the human corpus callosum (where CC scores are divided by an index of brain size). Future applications to human research are also discussed.


Endocrinology ◽  
2020 ◽  
Vol 161 (6) ◽  
Author(s):  
Sheryl E Arambula ◽  
Margaret M McCarthy

Abstract Sex is an essential biological variable that significantly impacts multiple aspects of neural functioning in both the healthy and diseased brain. Sex differences in brain structure and function are organized early in development during the critical period of sexual differentiation. While decades of research establish gonadal hormones as the primary modulators of this process, new research has revealed a critical, and perhaps underappreciated, role of the neuroimmune system in sex-specific brain development. The immune and endocrine systems are tightly intertwined and share processes and effector molecules that influence the nervous system. Thus, a natural question is whether endocrine-immune crosstalk contributes to sexual differentiation of the brain. In this mini-review, we first provide a conceptual framework by classifying the major categories of neural sex differences and review the concept of sexual differentiation of the brain, a process occurring early in development and largely controlled by steroid hormones. Next, we describe developmental sex differences in the neuroimmune system, which may represent targets or mediators of the sexual differentiation process. We then discuss the overwhelming evidence in support of crosstalk between the neuroendocrine and immune systems and highlight recent examples that shape sex differences in the brain. Finally, we review how early life events can perturb sex-specific neurodevelopment via aberrant immune activation.


2001 ◽  
Vol 7 (7) ◽  
pp. 904-905
Author(s):  
Barbara R. Sherman

Sexual Differentiation of the Brain will appeal primarily to researchers with specific interest in neuroendocrinological contributions to the sexual dimorphism of brain structures and neuropathways, predominantly in nonhumans. Collectively, the 16 chapters provide comprehensive review of our current understanding of the effects of hormonal steroids and their metabolites on brain development and the manner in which this correlates with specific behavioral functions. The clinician interested in furthering an understanding of sexually differentiated cognitive functioning or behavioral patterns in humans, may perceive discussion in many chapters as esoteric at best, or less charitably, as irrelevant. It is assumed that the reader has a prerequisite understanding of basic genetic and hormonal influences on brain development and subsequent behavioral manifestation. Although these issues are clarified by reference or associated discussion in several chapters, an introductory overview by the editor would have been beneficial. Similarly, the editor would have facilitated the reader's effort by organizing chapters according to findings of brain sexual dimorphism in humans versus “primitive” species, by clarifying the relevance of examining other species and/or by focusing attention to parallels in anatomical findings or in associated behavior.


Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Jordyn M. Stuart ◽  
Jason J. Paris ◽  
Cheryl Frye ◽  
Heather B. Bradshaw

Background. Endogenous cannabinoids (eCBs) are involved in the development and regulation of reproductive behaviors. Likewise, prostaglandins (PGs) drive sexual differentiation and initiation of ovulation. Here, we use lipidomics strategies to test the hypotheses that mating immediately activates the biosynthesis and/or metabolism of eCBs and PGs and that specific mating strategies differentially regulate these lipids in the brain.Methods. Lipid extractions and tandem mass spectrometric analysis were performed on brains from proestrous rats that had experienced one of two mating strategies (paced or standard mating) and two nonmated groups (chamber exposed and home cage controls). Levels of PGs (PGE2 and PGF2alpha), eCBs (AEA and 2-AG,N-arachidonoyl glycine), and 4 related lipids (4N-acylethanolamides) were measured in olfactory bulb, hypothalamus, hippocampus, thalamus, striatum, midbrain, cerebellum, and brainstem.Results. Overall, levels of these lipids were significantly lower among paced compared to standard mated rats with the most dramatic decreases observed in brainstem, hippocampus, midbrain, and striatum. However, chamber exposed rats had significantly higher levels of these lipids compared to home cage controls and paced mated wherein the hippocampus showed the largest increases.Conclusions. These data demonstrate that mating strategies and exposure to mating arenas influence lipid signaling in the brain.


Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.


2014 ◽  
Vol 9 (2) ◽  
pp. 154-164 ◽  
Author(s):  
Danya Glaser

Purpose – The purpose of this paper is to outline brain structure and development, the relationship between environment and brain development and implications for practice. Design/methodology/approach – The paper is based on a selected review of the literature and clinical experience. Findings – While genetics determine the sequence of brain maturation, the nature of brain development and functioning is determined by the young child's caregiving environment, to which the developing brain constantly adapts. The absence of input during sensitive periods may lead to later reduced functioning. There is an undoubted immediate equivalence between every mind function – emotion, cognition, behaviour and brain activity, although the precise location of this in the brain is only very partially determinable, since brain connections and function are extremely complex. Originality/value – This paper provides an overview of key issues in neurodevelopment relating to the development of young children, and implications for policy and practice.


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