scholarly journals Neuroendocrine-Immune Crosstalk Shapes Sex-Specific Brain Development

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.

1985 ◽  
Vol 63 (6) ◽  
pp. 577-594 ◽  
Author(s):  
Roger A. Gorski

The mammalian brain appears to be inherently feminine and the action of testicular hormones during development is necessary for the differentiation of the masculine brain both in terms of functional potential and actual structure. Experimental evidence for this statement is reviewed in this discussion. Recent discoveries of marked structural sex differences in the central nervous system, such as the sexually dimorphic nucleus of the preoptic area in the rat, offer model systems to investigate potential mechanisms by which gonadal hormones permanently modify neuronal differentiation. Although effects of these steroids on neurogenesis and neuronal migration and specification have not been conclusively eliminated, it is currently believed, but not proven, that the principle mechanism of steroid action is to maintain neuronal survival during a period of neuronal death. The structural models of the sexual differentiation of the central nervous system also provide the opportunity to identify sex differences in neurochemical distribution. Two examples in the rat brain are presented: the distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus and of tyrosine hydroxylase-immunoreactive fibers and cells in the anteroventral periventricular nucleus. It is likely that sexual dimorphisms will be found to be characteristic of many neural and neurochemical systems. The final section of this review raises the possibility that the brain of the adult may, in response to steroid action, be morphologically plastic, and considers briefly the likelihood that the brain of the human species is also influenced during development by the hormonal environment.


2016 ◽  
Vol 371 (1688) ◽  
pp. 20150451 ◽  
Author(s):  
Daphna Joel ◽  
Anne Fausto-Sterling

In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being.


1993 ◽  
Vol 10 (1) ◽  
pp. 2-5
Author(s):  
Lesley J. Rogers

AbstractCurrently there is an increase in the number of articles published in scientific journals and in the popular scientific media that claim a biological basis for sex differences in cognition and in certain structures in the brain. It can be argued that there is over-emphasis on the differences rather than similarities between the sexes, but it is even more important to question the assumed causation of the differences. This paper discusses recent evidence for an interactive role of early experience and hormonal condition in determining sex differences in brain structure and function. Although early studies using rats were thought to show that the male sex hormone, testosterone, acts on the brain in early life to direct its differentiation into either the male or female form, it is know known that this result comes about indirectly by changing the mother’s behaviour towards the pups. The hormone does not act on the brain directly but rather it alters the environment in which the young animals are rasied and this, in turn, influences the development of the brain. Indeed, the brain is in dynamic register with its environment both during development and in adulthood. Other examples also show that old ideas of rigid biological determination of brain structure and function need to be laid aside.The hypotheses for hormonal causation of sex differences humans rely heavily, if not exclusively, on the earlier interpretation of the experiments with rats, and there seems to be resistance to changing these notions based on the new discoveries. Apparently, there is strong pressure to cling on to biological determinist theories for sex differences in behaviour, and this has profound effects on social and educational policy. For example, biological determinism has been used to justify under representation of women in certain professions. Realisation of the dramatic effects that environmental stimulation and learning can have on the development of brain and behaviour leads us to an optimistic position for social change towards equality for women.


CNS Spectrums ◽  
2001 ◽  
Vol 6 (1) ◽  
pp. 75-88 ◽  
Author(s):  
Gerianne M. Alexander ◽  
Bradley S. Peterson

AbstractIn a variety of mammalian species, prenatal androgens organize brain structures and functions that are later activated by steroid hormones in postnatal life. In humans, studies of individuals with typical and atypical development suggest that sex differences in reproductive and nonreproductive behavior derive in part from similar prenatal and postnatal steroid effects on brain development. This paper provides a summary of research investigating hormonal influences on human behavior and describes how sex differences in the prevalences and natural histories of developmental psychopathologies may be consistent with these steroid effects. An association between patterns of sexual differentiation and specific forms of psychopathology suggests novel avenues for assessing the effects of sex steroids on brain structure and function, which may in turn improve our understanding of typical and atypical development in women and men.


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.


2010 ◽  
Vol 5 (4) ◽  
pp. 391-400 ◽  
Author(s):  
Denise C. Park ◽  
Chih-Mao Huang

There is clear evidence that sustained experiences may affect both brain structure and function. Thus, it is quite reasonable to posit that sustained exposure to a set of cultural experiences and behavioral practices will affect neural structure and function. The burgeoning field of cultural psychology has often demonstrated the subtle differences in the way individuals process information—differences that appear to be a product of cultural experiences. We review evidence that the collectivistic and individualistic biases of East Asian and Western cultures, respectively, affect neural structure and function. We conclude that there is limited evidence that cultural experiences affect brain structure and considerably more evidence that neural function is affected by culture, particularly activations in ventral visual cortex—areas associated with perceptual processing.


2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.


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.


2019 ◽  
Author(s):  
Madeline Farber ◽  
Dylan Gee ◽  
Ahmad R. Hariri

Studies of early adversity such as trauma, abuse, and neglect highlight the critical importance of quality caregiving in brain development and mental health. However, the impact of normative range variability in caregiving on such biobehavioral processes remains poorly understood. Thus, we lack an essential foundation for understanding broader, population-representative developmental mechanisms of risk and resilience. Here, we conduct a scoping review of the extant literature centered on the question, “Is variability in normative range parenting associated with variability in brain structure and function?” After removing duplicates and screening by title, abstract, and full-text, 23 records were included in a qualitative review. The most striking outcome of this review was not only how few studies have explored associations between brain development and normative range parenting, but also how little methodological consistency exists across published studies. In light of these limitations, we propose recommendations for future research on normative range parenting and brain development. In doing so, we hope to facilitate evidence-based research that will help inform policies and practices that yield optimal developmental trajectories and mental health.


2018 ◽  
Author(s):  
Kathryn L. Mills ◽  
Christian K. Tamnes

The development of the human brain involves a prolonged course of maturation, enabling us to learn to navigate our complex social environments. Here, we give short introductions to post-mortem and animal studies on postnatal brain development and selected methodological considerations for longitudinal developmental neuroimaging. We then describe typical developmental changes in brain structure and function from childhood to adulthood. We focus on measurements derived from magnetic resonance imaging (MRI) and on longitudinal data. Specifically, we discuss brain structural development based on morphometry and diffusion tensor imaging (DTI) studies, and functional development based on resting-state and task-based functional MRI. Finally, we highlight selected current overarching research questions and argue that an important step in answering these questions is to study individual differences in longitudinal brain development.


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