Publications of Jacques Balthazart
Sex steroid-induced neuroplasticity and behavioral activation in birds
Balthazart, Jacques ; Charlier, Thierry ; Barker, Jennifer et al
in European Journal of Neuroscience (2010), 32Detailed reference viewed: 24 (6 ULg)
Neuroplasticity and steroid-dependent male sexual behavior modulated by steroid receptor coactivator 2 (SRC2) in Japanese quail (Coturnix japonica).
Niessen, Neville-Andrew ; Balthazart, Jacques ; et al
Poster (2010)Detailed reference viewed: 13 (3 ULg)
Expression of the steroid receptor coactivators SRC-1 and CARM1 is modulated during different phases of neurogenesis in the dentate gyrus of adult female rats
Charlier, Thierry ; ; Balthazart, Jacques et al
Poster (2010)Detailed reference viewed: 16 (1 ULg)
Rapid regulation of aromatase activity and the role of stress
; Charlier, Thierry ; Cornil, Charlotte et al
Poster (2010)Detailed reference viewed: 19 (2 ULg)
Own song selectivity in the songbird auditory pathway: suppression by norepinephrine
; ; et al
Poster (2010)Detailed reference viewed: 6 (0 ULg)
Cloning of the steroid receptor coactivator SRC-2 and distribution in the brain of Japanese quail
Niessen, Neville-Andrew ; Charlier, Thierry ; Balthazart, Jacques
Poster (2009)Detailed reference viewed: 16 (2 ULg)
Steroids and neuroprotection: New advances.
; Balthazart, Jacques
in Frontiers in Neuroendocrinology (2009), 30(2), -
Gonadal hormones exert neuroprotective actions. In addition, it has become evident that the local synthesis of these molecules in the central nervous system may prevent or reduce neurodegeneration.The ... [more ▼]
Gonadal hormones exert neuroprotective actions. In addition, it has become evident that the local synthesis of these molecules in the central nervous system may prevent or reduce neurodegeneration.The neuroprotective actions of steroids involve neurons, glial cells and blood vessels, are exerted via steroid receptor signaling initiated at the nuclear or membrane level and steroid receptor independent mechanisms. They include the regulation of phosphatases and kinases and the regulation of the expression of molecules controlling inflammation and apoptosis. In addition, mitochondria have emerged as new central targets for neuroprotective actions of steroids. These neuroprotective actions have been documented in different experimental models of neurological alterations, including motoneuron injury, Parkinson's disease, traumatic brain injury, multiple sclerosis, stroke and Alzheimer's disease. In addition, steroids promote serotonergic neuronal function and protect against affective disorders. This special issue of Frontiers in Neuroendocrinology contains a collection of reviews of the most recent ideas and findings on these various aspects of sex steroid-dependent neuroprotection [less ▲]Detailed reference viewed: 153 (2 ULg)
Sex differences in the expression of sex steroid receptor mRNA in the quail brain.
; ; Balthazart, Jacques
in Journal of Neuroendocrinology (2009)
Abstract In Japanese quail, males will readily exhibit the full sequence of male-typical sexual behaviors but females never show this response even after ovariectomy and treatment with male-typical ... [more ▼]
Abstract In Japanese quail, males will readily exhibit the full sequence of male-typical sexual behaviors but females never show this response even after ovariectomy and treatment with male-typical concentrations of exogenous testosterone. Testosterone aromatization plays a key-limiting role in the activation of this behavior but the higher aromatase activity in the brain of males compared to females is not sufficient to explain the behavioral sex difference. The cellular and molecular bases of this prominent sex difference in the functional consequences of testosterone have not been identified so far. We hypothesized that the differential expression of sex steroid receptors in specific brain areas could mediate this behavioral sex difference and therefore quantified by radioactive in situ hybridization histochemistry the expression of the mRNA coding for the androgen receptor (AR) and the estrogen receptors (ER) of the alpha and beta sub-types. All three receptors were expressed in an anatomically discrete manner in various nuclei of the hypothalamus and limbic system and, at usually lower densities, in a few other brain areas. In both sexes, the intensity of the hybridization signal for all steroid receptors was highest in the medial preoptic nucleus (POM), a major site of testosterone action related to the activation of male sexual behavior. Although no sex difference in the optical density of the AR hybridization signal could be found in POM, the area covered by AR mRNA was significantly larger in males than in females, indicating a higher overall degree of AR expression in this region in males. In contrast, females tended to have significantly higher levels of AR expression than males in the lateral septum. ERalpha was more densely expressed in females than males throughout the medial preoptic and hypothalamic areas (including the POM and the medio-basal hypothalamus [MBH)], an area implicated in the control of female receptivity) and in the mesencephalic nucleus intercollicularis. ERbeta was more densely expressed in the medio-basal hypothalamus of females but a difference in the reverse direction (males>females) was observed in the nucleus taeniae of the amygdala. These data suggest that a differential expression of steroid receptors in specific brain areas could mediate at least certain aspects of the sex differences in behavioral responses to testosterone but they do not appear to be sufficient to explain the complete lack of activation by testosterone of male-typical copulatory behavior in females. [less ▲]Detailed reference viewed: 57 (2 ULg)
Estradiol, a key endocrine signal in the sexual differentiation and activation of reproductive behavior in quail.
Balthazart, Jacques ; Cornil, Charlotte ; Charlier, Thierry et al
in Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology (2009), 311(5), 323-45
In Japanese quail, estrogen's effects on sexual behavior can be divided into three classes based on the underlying mechanisms and time-course of action and release. During embryonic life, the embryonic ... [more ▼]
In Japanese quail, estrogen's effects on sexual behavior can be divided into three classes based on the underlying mechanisms and time-course of action and release. During embryonic life, the embryonic ovary secretes large amounts of estrogens. In contrast to what is observed in mammals where sexual differentiation essentially proceeds via masculinization of the males, in quail, females are demasculinized by their endogenous ovarian estrogens, an effect that can be blocked by injection of an aromatase inhibitor and mimicked in male embryos by an injection of estradiol. In adulthood, testosterone secreted by the testes is converted into estrogens by the preoptic aromatase. Locally produced estrogens activate male sexual behavior largely through the activation of estrogen receptors resulting in the transcription of a variety of genes, including brain aromatase (genomic effect). Both changes in estrogen production and action are observed within latencies ranging from a few hours to a few days, and are completely reversible. Additionally, brain aromatase activity can be modulated within minutes by calcium-dependent phosphorylations, triggered by variations in glutamatergic neurotransmission. These rapid changes in aromatase activity affect with relatively short latencies (10-15 min) the expression of male sexual behavior in quail and also in mice. Overall, the effects of estrogens on sexual behavior can thus be categorized into three classes: organizational (irreversible genomic action during ontogeny), activational (reversible genomic action during adulthood) and rapid nongenomic effects. Rapid and slower changes in brain aromatase activity match well with the two modes of estrogen action on behavior and provide temporal variations in the estrogens' bioavailability that should be able to support the entire range of established effects for this steroid. [less ▲]Detailed reference viewed: 29 (11 ULg)
Species and tissue-independent rapid regulation of aromatase activity by phosphorylations.
Charlier, Thierry ; ; et al
in Acta Neurologica Belgica (2009)
Aromatase activity (AA) is rapidly inhibited in male quail brains, following expression of sexual behavior, activation of glutamatergic receptors or exposure to phosphorylating conditions. Questions ... [more ▼]
Aromatase activity (AA) is rapidly inhibited in male quail brains, following expression of sexual behavior, activation of glutamatergic receptors or exposure to phosphorylating conditions. Questions remain as to whether direct aromatase phosphorylation is the common key regulatory mechanism and whether these inhibitions are specific to quail hypothalamus. We now showed that AA is rapidly downregulated in quail ovary homogenates incubated in phosphorylating conditions, similarly to what is observed in hypothalamic homogenates. To understand the processes underlying this control, we expressed human aromatase in the human cell line HEK293 and 1) researched whether human aromatase can also be rapidly modulated by phosphorylations and 2) investigated more precisely the processes involved in this rapid control of activity. AA in HEK293 was rapidly inhibited following depolarization of intact cells with 100 mM KCl or in cell lysates exposed to phosphorylating conditions. Thus inhibition of AA in phosphorylating conditions is not unique to the quail hypothalamus neural environment but seems to be a general process. We are now defining the contribution of single residues of the aromatase protein to this enzymatic control. [less ▲]Detailed reference viewed: 17 (4 ULg)
The fast regulation of aromatase activity by phosphorylations is species and tissue-independent.
Charlier, Thierry ; ; et al
Poster (2009)Detailed reference viewed: 15 (1 ULg)
Species Differences in the Relative Densities of D1- and D2-Like Dopamine Receptor Subtypes in the Japanese Quail and Rats: An in vitro Quantitative Receptor Autoradiography Study.
; Cornil, Charlotte ; Balthazart, Jacques et al
in Brain, Behavior & Evolution (2009), 73(2), 81-90
Evidence has accumulated that the regulation of male sexual behavior by dopamine might not be the same in Japanese quail (and perhaps all birds) as it is in mammals. For example, the non-selective ... [more ▼]
Evidence has accumulated that the regulation of male sexual behavior by dopamine might not be the same in Japanese quail (and perhaps all birds) as it is in mammals. For example, the non-selective dopamine receptor agonist, apomorphine (APO), facilitates male sexual behavior in rats but inhibits it in quail. Although the general organization of the dopamine system is similar in birds and mammals, it is possible that the relative distribution and/or density of binding sites are different. We therefore compared the relative densities of D1-like and D2-like receptor subtypes in Japanese quail and rats, with the use of in vitro quantitative receptor autoradiography. Brain sections from 8 male rats and 8 male quail were labeled with [(3)H]SCH-23390 and [(3)H]Spiperone. In general we found a systematic species difference in the relative density of D1- vs. D2-like receptors such that the D2/D1 ratio is higher in quail than in rats in areas, known to be important target sites for dopamine action such as striatal regions or the preoptic area, which is also associated with activation of sexual behavior. This difference might explain the variation in the behavioral effectiveness of APO in rats as compared to quail; with a higher relative density of D2-like receptors in quail, a similar dose of APO would be more likely to activate inhibitory processes in quail than in rats. [less ▲]Detailed reference viewed: 25 (1 ULg)
Behavioral effects of brain-derived estrogens in birds.
Balthazart, Jacques ; Taziaux, Mélanie ; et al
in Annals of the New York Academy of Sciences (2009), 1163
In birds as in other vertebrates, estrogens produced in the brain by aromatization of testosterone have widespread effects on behavior. Research conducted with male Japanese quail demonstrates that ... [more ▼]
In birds as in other vertebrates, estrogens produced in the brain by aromatization of testosterone have widespread effects on behavior. Research conducted with male Japanese quail demonstrates that effects of brain estrogens on all aspects of sexual behavior, including appetitive and consummatory components as well as learned aspects, can be divided into two main classes based on their time course. First, estrogens via binding to estrogen receptors regulate the transcription of a variety of genes involved primarily in neurotransmission. These neurochemical effects ultimately result in the activation of male copulatory behavior after a latency of a few days. Correlatively, testosterone and its aromatized metabolites increase the transcription of the aromatase mRNA, resulting in an increased concentration and activity of the enzyme that actually precedes behavioral activation. Second, recent studies with quail demonstrate that brain aromatase activity can also be modulated within minutes by phosphorylation processes regulated by changes in intracellular calcium concentration, such as those associated with glutamatergic neurotransmission. The rapid upregulations or downregulations of brain estrogen concentration (presumably resulting from these changes in aromatase activity) affect, by nongenomic mechanisms with relatively short latencies (frequency increases or decreases respectively within 10-15 min), the expression of male sexual behavior in quail and also in rodents. Brain estrogens thus affect behavior on different time scales by genomic and nongenomic mechanisms similar to those of a hormone or a neurotransmitter. [less ▲]Detailed reference viewed: 29 (3 ULg)
Complex modulation of singing behavior by testosterone in an open-ended learner, the European Starling.
; ; Balthazart, Jacques et al
in Hormones & Behavior (2009), 56(5), 564-73
In many temperate zone songbird species males only produce song during the breeding season, when plasma testosterone (T) levels are high. Males of some species sing throughout the year, even when T levels ... [more ▼]
In many temperate zone songbird species males only produce song during the breeding season, when plasma testosterone (T) levels are high. Males of some species sing throughout the year, even when T levels are low, indicating a dissociation between high T levels and song rate. Given that few studies have taken advantage of these species, we compare here song traits expressed under high versus low T concentrations and we study the role of testosterone in adult song learning in the European Starling, an open-ended learner in which repertoire size dramatically increases with age. We performed a detailed comparison of song complexity and song rate between fall and spring in 6-year-old intact male European starlings. In parallel, we investigated whether potential seasonal changes were regulated by the gonadally induced increase in plasma T, by comparing seasonal changes in intact and castrated males of the same age (castrated as juveniles during their first fall) and by subsequently experimentally elevating T in half of the castrated males. While song rate and stereotypy did not differ between intacts and castrates or between fall and spring, both groups increased their average song bout length from fall to spring, but only intact males increased their repertoire size, indicating that effects of seasonal T changes differ between song traits. Intact males overall displayed a larger song repertoire and a longer bout length than the castrates, and implantation with T caused a turnover in repertoire composition in castrates. However, as the castrates had never experienced high T levels and yet displayed a markedly higher repertoire size than that of typical yearling males, this suggests that the progressive increase of song repertoire with age in male starlings is not dependent on gonadal T, although it may be T-enhanced. [less ▲]Detailed reference viewed: 73 (1 ULg)
Presence of aromatase and estrogen receptor alpha in the inner ear of zebra finches.
Noirot, Isabelle ; ; Cornil, Charlotte et al
in Hearing Research (2009)
Sex differences in song behavior and in the neural system controlling song in songbirds are well documented but relatively little is known about sex differences in hearing. We recently demonstrated the ... [more ▼]
Sex differences in song behavior and in the neural system controlling song in songbirds are well documented but relatively little is known about sex differences in hearing. We recently demonstrated the existence of sex differences in auditory brainstem responses in a songbird species, the zebra finch (Taeniopygia guttata). Many sex differences are regulated by sex steroid hormone action either during ontogeny or in adulthood. As a first step to test the possible implication of sex steroids in the control of sex differences in the zebra finch auditory system, we evaluated via immunocytochemistry whether estrogens are produced and act in the zebra finch inner ear. Specifically we examined the distribution of aromatase, the enzyme converting testosterone into an estrogen, and of estrogen receptors of the alpha subtype (ERalpha) in adult zebra finch inner ears. The anatomy of the basilar papillae was visualized by fluorescein-phalloidin, which delineated the actin structure of hair cells and supporting cells at their apical surface. Whole mount preparations of basilar papillae stained by immunocytochemistry revealed in both males and females an abundant aromatase distribution in the cytoplasm of hair cells, while ERalpha was identified in the nuclei of hair cells and of underlying supporting cells. Double labeled preparations confirmed the extensive co-localization of aromatase and ERalpha in the vast majority of the hair cells. These results are consistent with studies on non-avian species, suggesting a role for estrogens in auditory function. These findings are also consistent with the notion that estrogens may contribute to a sex difference in hearing. To our knowledge, this is the first demonstration of the presence of aromatase and of the co-localization of aromatase and ERalpha in the sensory epithelium of the inner ear in any animal model. [less ▲]Detailed reference viewed: 83 (11 ULg)
MRI in small brains displaying extensive plasticity.
; ; et al
in Trends in Neurosciences (2009)
Manganese-enhanced magnetic resonance imaging (ME-MRI), blood oxygen-level-dependent functional MRI (BOLD fMRI) and diffusion tensor imaging (DTI) can now be applied to animal species as small as mice or ... [more ▼]
Manganese-enhanced magnetic resonance imaging (ME-MRI), blood oxygen-level-dependent functional MRI (BOLD fMRI) and diffusion tensor imaging (DTI) can now be applied to animal species as small as mice or songbirds. These techniques confirmed previous findings but are also beginning to reveal new phenomena that were difficult or impossible to study previously. These imaging techniques will lead to major technical and conceptual advances in systems neurosciences. We illustrate these new developments with studies of the song control and auditory systems in songbirds, a spatially organized neuronal circuitry that mediates the acquisition, production and perception of complex learned vocalizations. This neural system is an outstanding model for studying vocal learning, brain steroid hormone action, brain plasticity and lateralization of brain function. [less ▲]Detailed reference viewed: 34 (10 ULg)
Own-song recognition in the songbird auditory pathway: selectivity and lateralization.
; ; et al
in Journal of Neuroscience (2009), 29(7), 2252-8
The songbird brain is able to discriminate between the bird's own song and other conspecific songs. Determining where in the brain own- song selectivity emerges is of great importance because experience ... [more ▼]
The songbird brain is able to discriminate between the bird's own song and other conspecific songs. Determining where in the brain own- song selectivity emerges is of great importance because experience-dependent mechanisms are necessarily involved and because brain regions sensitive to self-generated vocalizations could mediate auditory feedback that is necessary for song learning and maintenance. Using functional MRI, here we show that this selectivity is present at the midbrain level. Surprisingly, the selectivity was found to be lateralized toward the right side, a finding reminiscent of the potential right lateralization of song production in zebra finches but also of own-face and own-voice recognition in human beings. These results indicate that a midbrain structure can process subtle information about the identity of a subject through experience-dependent mechanisms, challenging the classical perception of subcortical regions as primitive and nonplastic structures. They also open questions about the evolution of the cognitive skills and lateralization in vertebrates. [less ▲]Detailed reference viewed: 54 (5 ULg)
Doublecortin as a Marker of Adult Neuroplasticity in the Canary Song Control Nucleus Hvc
Balthazart, Jacques ; Boseret, Géraldine ; et al
in European Journal of Neuroscience (2008), 27(4), 801-17
It is established that in songbirds the size of several brain song control nuclei varies seasonally, based on changes in cell size, dendritic branching and, in nucleus HVC, the incorporation of newborn ... [more ▼]
It is established that in songbirds the size of several brain song control nuclei varies seasonally, based on changes in cell size, dendritic branching and, in nucleus HVC, the incorporation of newborn neurons. In the developing and adult mammalian brain, the protein doublecortin (DCX) is expressed in postmitotic neurons and, as a part of the microtubule machinery, required for neuronal migration. We recently showed that in adult canaries, DCX-immunoreactive (ir) cells are present throughout the telencephalon, but the link between DCX and the active neurogenesis observed in songbirds remained uncertain. We demonstrate here that DCX labels recently born cells in the canary telencephalon and that, in parallel with changes in HVC volume, the number of DCX-ir cells is increased specifically in the HVC of testosterone-treated males compared with castrates, and in castrated testosterone-treated males paired with a female as compared with males paired with another male. The numbers of elongated DCX-ir cells (presumptive migrating neurons) and round multipolar DCX-ir cells (differentiating neurons) were also affected by the sex of the subjects and their photoperiodic condition (photosensitive vs photostimulated vs photorefractory). Thus, in canaries the endocrine state, as well as the social or photoperiodic condition independently of variation in steroid hormone action, affects the number of cells expressing a protein involved in neuronal migration specifically in brain areas that incorporate new neurons in the telencephalon. The DCX gene may be one of the targets by which testosterone and social stimuli induce seasonal changes in the volume of song nuclei. [less ▲]Detailed reference viewed: 40 (4 ULg)
The underestimated role of olfaction in avian reproduction?
Balthazart, Jacques ; Taziaux, Mélanie
in Behavioural Brain Research (2008)
Until the second half of the 20th century, it was broadly accepted that most birds are microsmatic if not anosmic and unable to detect and use olfactory information. Exceptions were eventually conceded ... [more ▼]
Until the second half of the 20th century, it was broadly accepted that most birds are microsmatic if not anosmic and unable to detect and use olfactory information. Exceptions were eventually conceded for species like procellariiforms, vultures or kiwis that detect their food at least in part based on olfactory signals. During the past 20-30 years, many publications have appeared indicating that this view is definitely erroneous. We briefly review here anatomical, electrophysiological and behavioral data demonstrating that birds in general possess a functional olfactory system and are able to use olfactory information in a variety of ethological contexts, including reproduction. Recent work also indicates that brain activation induced by sexual interactions with a female is significantly affected by olfactory deprivation in Japanese quail. Brain activation was measured via immunocytochemical detection of the protein product of the immediate early gene c-fos. Changes observed concerned two brain areas that play a key role in the control of male sexual behavior, the medial preoptic nucleus and the bed nucleus of the stria terminalis therefore suggesting a potential role of olfaction in the control of reproduction. The widespread idea that birds are anosmic or microsmatic is thus not supported by the available experimental data and presumably originates in our anthropomorphic view that leads us to think that birds do not smell because they have a rigid beak and nostrils and do not obviously sniff. Experimental analysis of this phenomenon is thus warranted and should lead to a significant change in our understanding of avian biology. [less ▲]Detailed reference viewed: 45 (4 ULg)
localized modulation of testosterone action: Function of steroid receptor coactivators in the brain
Charlier, Thierry ; Balthazart, Jacques
in Ardis, L. I. (Ed.) New research on testosterone (2008)
Testosterone, through its activation of androgen and estrogen receptors, has been shown to play a critical role in brain development and physiology. Recent studies have shown that the activity of these ... [more ▼]
Testosterone, through its activation of androgen and estrogen receptors, has been shown to play a critical role in brain development and physiology. Recent studies have shown that the activity of these receptors can be modulated by the interaction with several proteins and, in particular, that coactivators are required to enhance their transcriptional activity. The steroid receptor coactivator-1, SRC-1 is the best-characterized coactivator and we review here the current knowledge on the distribution, regulation of expression and function of this protein in the brain, focusing mostly on our work in Japanese quail. As expected for a ubiquitous coactivator, SRC-1 is present throughout the brain in both mammalian and avian species but is found in particularly high concentrations in testosterone-sensitive areas such as the preoptic area in rat and Japanese quail and in the song control nuclei in songbirds. Further analysis demonstrates that the expression of SRC-1 is not constitutive but regulated in specific brain areas by the sex, acute stress and testosterone treatment. In addition, the protein concentration appears to fluctuate through the day in some brain regions. These modulations of SRC-1 expression by endogenous (sex) and exogenous (stress) factors could potentially exacerbate at specific times the competition or squelching between different nuclear receptors and therefore decrease the biological response induced by one or another hormonal system. Although the existence of such a phenomenon has not yet been demonstrated in a functionally intact biological system, the effects of SRC-1 antisense treatments clearly strengthen this hypothesis. Indeed, the decrease of SRC-1 expression in the hypothalamus induced by antisense oligonucleotide injections clearly inhibited both estrogen-dependent male sexual behavior and androgen-dependent pre- and post-copulatory displays (strut) in Japanese quail, therefore demonstrating a role of the coactivator in the transcriptional activation induced by both estrogen and androgen receptors. Interestingly, the inhibitory effect on sexual behavior of SRC-1 knock down was not systematically associated with modifications of several histological (definition of median preoptic nucleus [POM] using Nissl staining), immunohistochemical (aromatase and vasotocin cells and fibers in the POM) and biochemical (aromatase enzymatic activity) markers of testosterone action in the brain. This dissociation of the effects of SRC-1 on behavior on the one hand and on aromatase and POM neurochemistry on another hand suggests that other system(s) involved in the activation of male sexual behavior are likely more sensitive to a decrease of SRC-1 expression. In future research, it will be essential to determine the other cofactors involved in specific physiological responses and to define whether these coactivators act synergistically, in parallel or independently in the modulation of the activity of one or several nuclear receptors linked to a particular physiological event. In several biological models, the observed changes in concentration of the circulating hormone and /or its receptors are apparently not sufficient to explain the physiological and behavioral responses observed after testosterone treatment. The discovery of steroid receptor coactivators opens new perspectives in the study of the molecular basis of steroid action at the level of the organism and a complete understanding of the mechanisms of steroid action will not be achieved without a detailed characterization of nuclear receptor cofactors. [less ▲]Detailed reference viewed: 44 (3 ULg)