scholarly journals Sex Steroids and the Shaping of the Peripubertal Brain: The Sexual-Dimorphic Set-Up of Adult Neurogenesis

2021 ◽  
Vol 22 (15) ◽  
pp. 7984
Author(s):  
Sara Trova ◽  
Serena Bovetti ◽  
Sara Bonzano ◽  
Silvia De Marchis ◽  
Paolo Peretto

Steroid hormones represent an amazing class of molecules that play pleiotropic roles in vertebrates. In mammals, during postnatal development, sex steroids significantly influence the organization of sexually dimorphic neural circuits underlying behaviors critical for survival, such as the reproductive one. During the last decades, multiple studies have shown that many cortical and subcortical brain regions undergo sex steroid-dependent structural organization around puberty, a critical stage of life characterized by high sensitivity to external stimuli and a profound structural and functional remodeling of the organism. Here, we first give an overview of current data on how sex steroids shape the peripubertal brain by regulating neuroplasticity mechanisms. Then, we focus on adult neurogenesis, a striking form of persistent structural plasticity involved in the control of social behaviors and regulated by a fine-tuned integration of external and internal cues. We discuss recent data supporting that the sex steroid-dependent peripubertal organization of neural circuits involves a sexually dimorphic set-up of adult neurogenesis that in turn could be relevant for sex-specific reproductive behaviors.

2002 ◽  
Vol 92 (2) ◽  
pp. 493-503 ◽  
Author(s):  
Deborah N. D'Souza ◽  
Richard E. Harlan ◽  
Meredith M. Garcia

Rats show gender differences in responses to morphine and the N-methyl-d-aspartate receptor antagonist dizocilpine (MK-801); the role of sex steroids in mediating these differences is unclear. We tested the overall hypothesis that circulating gonadal steroids determine the gender differences in morphine- and MK-801-induced behavior and c-Fos expression. Morphine caused a greater expression of c-Fos in the striatum of intact males than of that females, which was independent of sex steroids. MK-801 completely inhibited morphine-induced c-Fos in intact females but only caused partial inhibition in intact males; castrated males showed complete inhibition, which was reversed by testosterone, but gonadal steroids had no effect on this response in females. In thalamus, there was a large sex difference in the response to MK-801 that was independent of gonadal steroids. Behavioral responses to morphine were greater in males, but responses to MK-801 were greater in females; both were sex steroid independent. These findings show significant sex differences in response to morphine and MK-801 that are mediated by sex steroid-dependent and -independent mechanisms, which may be important in treatment outcomes of drug addiction.


2020 ◽  
Vol 14 ◽  
Author(s):  
Sara Trova ◽  
Serena Bovetti ◽  
Giuliana Pellegrino ◽  
Sara Bonzano ◽  
Paolo Giacobini ◽  
...  

Adult neurogenesis, a striking form of neural plasticity, is involved in the modulation of social stimuli driving reproduction. Previous studies on adult neurogenesis have shown that this process is significantly modulated around puberty in female mice. Puberty is a critical developmental period triggered by increased secretion of the gonadotropin releasing hormone (GnRH), which controls the activity of the hypothalamic-pituitary-gonadal axis (HPG). Secretion of HPG-axis factors at puberty participates to the refinement of neural circuits that govern reproduction. Here, by exploiting a transgenic GnRH deficient mouse model, that progressively loses GnRH expression during postnatal development (GnRH::Cre;DicerloxP/loxPmice), we found that a postnatally-acquired dysfunction in the GnRH system affects adult neurogenesis selectively in the subventricular-zone neurogenic niche in a sexually dimorphic way. Moreover, by examining adult females ovariectomized before the onset of puberty, we provide important evidence that, among the HPG-axis secreting factors, the circulating levels of gonadal hormones during pre-/peri-pubertal life contribute to set-up the proper adult subventricular zone-olfactory bulb neurogenic system.


1989 ◽  
Vol 122 (2) ◽  
pp. 573-581 ◽  
Author(s):  
B. A. Schlinger ◽  
A. J. Fivizzani ◽  
G. V. Callard

ABSTRACT While intrasexual competition for mates is generally considered to be an androgen-dependent characteristic of reproductively active males, in the Wilson's phalarope (Phalaropus tricolor) it is the female that acquires the brighter nuptial plumage and aggressively competes for access to the less aggressive males. Despite this pronounced sex-role reversal, circulating sex steroid hormones of breeding phalaropes are similar to those of avian species displaying traditional male–female reproductive roles. To investigate whether these behavioural and morphological steroid-dependent differences may be due to differences in target organ metabolism of circulating androgen, [3H]androstenedione in the presence of an NADPH-generating system was incubated with homogenates of brain, pituitary and skin of male and female Wilson's phalaropes collected from a naturally breeding population. Oestrone, 5α-androstanedione and 5β-androstanedione were measured as endpoints of aromatization, 5α-reduction and 5β-reduction respectively. Aromatase activity in the anterior hypothalamus/preoptic area (AHPOA) and posterior hypothalamus was greater in breeding males with high circulating concentrations of testosterone than in females, and activity in the AHPOA was greater in breeding than in non-breeding males (with low circulating testosterone). Aromatase levels did not differ in septum, archistriatum, hyperstriatum or pituitary. 5α- and 5β-reductase were detected in all neuroendocrine tissues sampled and although there were no significant male–female differences, 5α-reductase was greater in the AHPOA of breeding than of non-breeding males. We infer from this that the behavioural sex-role reversal of phalaropes is unlikely to be accounted for by differences in androgen metabolism in neural targets, although the capacity to form greater quantities of oestrogenic and 5α-reduced metabolites in the AHPOA of breeding males may be linked to the expression of masculine copulatory behaviours. Aromatase activity was not detected in skin containing a sexually dimorphic feather tract; however, 5α- and 5β-reductase activities were significantly higher in females than in males and may account for the brighter nuptial plumage of females. These data suggest that alternate determinants of neural responsiveness such as sex-steroid receptor abundance or neural circuitry may underlie atypical sexual behaviours in phalaropes. Journal of Endocrinology (1989) 122, 573–581


2006 ◽  
Vol 290 (5) ◽  
pp. E1006-E1013 ◽  
Author(s):  
Thomas Münzer ◽  
Clifford J. Rosen ◽  
S.Mitchell Harman ◽  
Katherine M. Pabst ◽  
Carol St. Clair ◽  
...  

Circulating GH, IGF-I, IGFBP-3, and sex steroid concentrations decrease with age. GH or sex steroid treatment increases IGFBP-3, but little is known regarding the effects of these hormones on other IGFBPs. We assessed the effects of 26 wk of administration of GH, sex steroids, or GH + sex steroids on AM levels of IGF-I, IGFBPs 1–5, insulin, glucose, and osteocalcin and 2-h urinary excretion of deoxypyridinolline (DPD) cross-links in 53 women and 71 men aged 65–88 yr. Before treatment, in women and men, IGF-I was directly related to IGFBP-3 ( P < 0.001 and P < 0.0001) and IGFBP-1 to IGFBP-2 ( P = 0.0001). In women, IGFBP-1 was inversely related to insulin ( P < 0.0005) and glucose ( P < 0.005) and IGFBP-4 to osteocalcin ( P < 0.01). IGFBP-4 and IGFBP-5 were not significantly related to DPD cross-links. GH and/or sex steroid increased IGF-I levels in both sexes, with higher concentrations in men ( P < 0.001). In women, the IGF-I increment after GH was attenuated by hormone replacement therapy (HRT) coadministration ( P < 0.05). Hormone administration also increased IGFBP-3. IGFBP-1 was unaffected by GH + sex steroids, whereas GH decreased IGFBP-2 by 15% in men ( P < 0.05). Hormone administration did not change IGFBP-4, whereas in men IGFBP-5 increased by 20% after GH ( P < 0.05) and 56% after GH + testosterone ( P = 0.0003). These data demonstrate sexually dimorphic IGFBP responses to GH. Additonally, HRT attenuated or prevented GH-mediated increases in IGF-I and IGFBP-3. Whether GH and/or sex steroid administration alters local tissue production of IGFBPs and whether the latter influence autocrine or paracrine actions of IGF-I remain to be determined.


2016 ◽  
Vol 371 (1688) ◽  
pp. 20150109 ◽  
Author(s):  
Daniel W. Bayless ◽  
Nirao M. Shah

The unique hormonal, genetic and epigenetic environments of males and females during development and adulthood shape the neural circuitry of the brain. These differences in neural circuitry result in sex-typical displays of social behaviours such as mating and aggression. Like other neural circuits, those underlying sex-typical social behaviours weave through complex brain regions that control a variety of diverse behaviours. For this reason, the functional dissection of neural circuits underlying sex-typical social behaviours has proved to be difficult. However, molecularly discrete neuronal subpopulations can be identified in the heterogeneous brain regions that control sex-typical social behaviours. In addition, the actions of oestrogens and androgens produce sex differences in gene expression within these brain regions, thereby highlighting the neuronal subpopulations most likely to control sexually dimorphic social behaviours. These conditions permit the implementation of innovative genetic approaches that, in mammals, are most highly advanced in the laboratory mouse. Such approaches have greatly advanced our understanding of the functional significance of sexually dimorphic neural circuits in the brain. In this review, we discuss the neural circuitry of sex-typical social behaviours in mice while highlighting the genetic technical innovations that have advanced the field.


2021 ◽  
Author(s):  
Przemysław Adamczyk ◽  
Martin Jáni ◽  
Tomasz S. Ligeza ◽  
Olga Płonka ◽  
Piotr Błądziński ◽  
...  

AbstractFigurative language processing (e.g. metaphors) is commonly impaired in schizophrenia. In the present study, we investigated the neural activity and propagation of information within neural circuits related to the figurative speech, as a neural substrate of impaired conventional metaphor processing in schizophrenia. The study included 30 schizophrenia outpatients and 30 healthy controls, all of whom were assessed with a functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG) punchline-based metaphor comprehension task including literal (neutral), figurative (metaphorical) and nonsense (absurd) endings. The blood oxygenation level-dependent signal was recorded with 3T MRI scanner and direction and strength of cortical information flow in the time course of task processing was estimated with a 64-channel EEG input for directed transfer function. The presented results revealed that the behavioral manifestation of impaired figurative language in schizophrenia is related to the hypofunction in the bilateral fronto-temporo-parietal brain regions (fMRI) and various differences in effective connectivity in the fronto-temporo-parietal circuit (EEG). Schizophrenia outpatients showed an abnormal pattern of connectivity during metaphor processing which was related to bilateral (but more pronounced at the left hemisphere) hypoactivation of the brain. Moreover, we found reversed lateralization patterns, i.e. a rightward-shifted pattern during metaphor processing in schizophrenia compared to the control group. In conclusion, the presented findings revealed that the impairment of the conventional metaphor processing in schizophrenia is related to the bilateral brain hypofunction, which supports the evidence on reversed lateralization of the language neural network and the existence of compensatory recruitment of alternative neural circuits in schizophrenia.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ben Somers ◽  
Christopher J. Long ◽  
Tom Francart

AbstractThe cochlear implant is one of the most successful medical prostheses, allowing deaf and severely hearing-impaired persons to hear again by electrically stimulating the auditory nerve. A trained audiologist adjusts the stimulation settings for good speech understanding, known as “fitting” the implant. This process is based on subjective feedback from the user, making it time-consuming and challenging, especially in paediatric or communication-impaired populations. Furthermore, fittings only happen during infrequent sessions at a clinic, and therefore cannot take into account variable factors that affect the user’s hearing, such as physiological changes and different listening environments. Objective audiometry, in which brain responses evoked by auditory stimulation are collected and analysed, removes the need for active patient participation. However, recording of brain responses still requires expensive equipment that is cumbersome to use. An elegant solution is to record the neural signals using the implant itself. We demonstrate for the first time the recording of continuous electroencephalographic (EEG) signals from the implanted intracochlear electrode array in human subjects, using auditory evoked potentials originating from different brain regions. This was done using a temporary recording set-up with a percutaneous connector used for research purposes. Furthermore, we show that the response morphologies and amplitudes depend crucially on the recording electrode configuration. The integration of an EEG system into cochlear implants paves the way towards chronic neuro-monitoring of hearing-impaired patients in their everyday environment, and neuro-steered hearing prostheses, which can autonomously adjust their output based on neural feedback.


2021 ◽  
Vol 13 (590) ◽  
pp. eabd6434
Author(s):  
Patrick Sweeney ◽  
Michelle N. Bedenbaugh ◽  
Jose Maldonado ◽  
Pauline Pan ◽  
Katelyn Fowler ◽  
...  

Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.


2013 ◽  
Vol 111 (4) ◽  
pp. 755-755
Author(s):  
Marianne A. Yon ◽  
Suzanna L. Mauger ◽  
Lucy C. Pickavance

Of the environmental factors which have an impact on body weight, nutrients are most influential. Within normal limits, hypothalamic and related neuronal populations correct perturbations in energy metabolism, to return the body to its nutritional set-point, either through direct response to nutrients or indirectly via peripheral appetite signals. Excessive intake of certain macronutrients, such as simple carbohydrates and SFA, can lead to obesity and attendant metabolic dysfunction, also reflected in alterations in structural plasticity, and, intriguingly, neurogenesis, in some of these brain regions. Neurogenesis, previously thought to occur only in the embryo, is now known to take place in the adult brain, dependent on numerous stimulating and inhibiting factors, including dietary components. Because of classic associations between neurogenesis and the hippocampus, in learning and cognition, this brain region has also been the focus of attention in the study of links between diet and neurogenesis. Recently, however, a more complete picture of this relationship has been building: not only has the hypothalamus been shown to satisfy the criteria for a neurogenic niche, but appetite-related mediators, including circulating hormones, such as leptin and ghrelin, pro-inflammatory cytokines and the endocannabinoid intracellular messengers, are also being examined for their potential role in mediating neurogenic responses to macronutrients. The present review draws together these observations and investigates whether n-3 PUFA may exert their attenuating effects on body weight through the stimulation of adult neurogenesis. Exploration of the effects of nutraceuticals on neurogenic brain regions may encourage the development of new rational therapies in the fight against obesity.


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