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See detailSexual behavior activates the expression of the immediate early genes c-fos and Zenk (egr-1) in catecholaminergic neurons of male Japanese quail.
Charlier, Thierry ULg; Ball, G. F.; Balthazart, Jacques ULg

in Neuroscience (2005), 131(1), 13-30

We analyzed the expression of the immediate early genes c-fos and Zenk (egr-1) in the brain of male quail that were gonadally intact (I) or castrated and treated (CX+T) or not (CX) with testosterone and ... [more ▼]

We analyzed the expression of the immediate early genes c-fos and Zenk (egr-1) in the brain of male quail that were gonadally intact (I) or castrated and treated (CX+T) or not (CX) with testosterone and had been exposed for 60 min either to a sexually mature female (F), or to an empty arena (EA) or were left in their home cage (HC). Alternate sections in the brains collected 90 min after the start of behavioral interactions were stained by immunocytochemistry for the proteins FOS or ZENK alone or in association with tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. C-fos and Zenk expression was statistically increased in six brain areas of sexually active birds (I+F, CX+T+F) compared with controls (CX+F, CX+T+EA, CX+T+HC), i.e. the preoptic area, bed nucleus striae terminalis, arcopallium, nucleus intercollicularis, periaqueductal gray and the ventral tegmental area. Interestingly, c-fos and Zenk expression was high in the nucleus intercollicularis, a midbrain vocal control nucleus, of I+F and CX+T+F birds that displayed copulatory behavior but emitted few crows but not in the nucleus intercollicularis of CX+T+EA birds that crowed frequently. Increases in c-fos expression were observed in TH-immunoreactive cells in the periaqueductal gray and ventral tegmental area, but not in the substantia nigra, of I+F and CX+T+F birds indicating the activation of dopaminergic neurons during sexual behavior. Together, these data confirm the implication of the steroid-sensitive preoptic area and bed nucleus striae terminalis in the control of copulation and support the notion that dopamine is involved in its control. [less ▲]

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See detailInhibition of steroid receptor coactivator-1 blocks estrogen and androgen action on male sex behavior and associated brain plasticity.
Charlier, Thierry ULg; Ball, Gregory F; Balthazart, Jacques ULg

in Journal of Neuroscience (2005), 25(4), 906-13

Studies of eukaryotic gene expression demonstrate the importance of nuclear steroid receptor coactivators in mediating efficient gene transcription. However, little is known about the physiological role ... [more ▼]

Studies of eukaryotic gene expression demonstrate the importance of nuclear steroid receptor coactivators in mediating efficient gene transcription. However, little is known about the physiological role of these coactivators in vivo. In Japanese quail, the steroid receptor coactivator-1 (SRC-1) is broadly expressed in steroid-sensitive brain areas that control the expression of male copulatory behavior, and we investigated the role of this coactivator by antisense technology. Daily intracerebroventricular injections of locked nucleic acid (LNA) antisense (AS) oligonucleotides targeting SRC-1 significantly reduced the expression of androgen- and estrogen-dependent male-typical sexual behaviors compared with control animals that received the vehicle alone or scrambled oligonucleotides. Sexual behavior was restored and even enhanced within 48 h after interruption of LNA injections. Western blot analysis confirmed the decrease of SRC-1 expression in AS animals and suggested an overexpression 48 h after the end of injections. The effects of SRC-1 knock-down on behavior correlated with a reduction in volume of the preoptic medial nucleus (POM) when its borders were defined by Nissl staining or by aromatase immunohistochemistry. The amount of aromatase-immunoreactive material in POM was also reduced in the AS compared with the control group. Previous work on SRC-1 knock-out mice raised questions about the importance of this specific coactivator in the regulation of reproductive behavior and development of sexually dimorphic structures in the CNS. Together, the present findings indicate that SRC-1 modulates steroid-dependent gene transcription and behavior and highlight the rapid time course of steroid-induced brain plasticity in adult quail. [less ▲]

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See detailDaily changes in the expression of the steroid receptor coactivator SRC-1.
Charlier, Thierry ULg; Ball, Gregory F.; Balthazart, Jacques ULg

in Hormones & Behavior (2005), 48

Steroid receptor coactivators such as SRC-1 significantly modulate the expression of steroid-dependent physiological and behavioral characteristics in birds and mammals. Changes in coactivator protein ... [more ▼]

Steroid receptor coactivators such as SRC-1 significantly modulate the expression of steroid-dependent physiological and behavioral characteristics in birds and mammals. Changes in coactivator protein expression are therefore likely to affect receptor-mediated transcriptional activity. We previously reported a tissue-dependent regulation of SRC-1 mRNA and protein levels by sex, stress and testosterone in the quail brain. In addition, SRC-1 expression has been shown to vary in mammals during development or in adulthood as a function of seasonal variation in photoperiod. We describe here tissue-specific changes of SRC-1 expression over the course of the day in quail. SRC-1 protein quantified by Western blots in the hindbrain gradually increased in the morning, reached a peak around midday and declined significantly in the afternoon. In contrast, SRC-1 protein levels in the optic lobes progressively decreased in the morning to reach their lowest values around midday before rising in the afternoon. The coactivator concentration in the hippocampus exhibited a progressive increase throughout the day. No change in the SRC-1 protein was detected during the day in the preoptic area and in the cerebellum. The functional significance and the mechanisms of regulation underlying such changes remain to be understood. An important unresolved question is whether this diurnal variation in SRC-1 expression is circadian in nature and if so if SRC-1 is an active player linked to clock genes in the generation of circadian rhythms or if the observed changes in SRC-1 expression are a consequence of the rhythms generated by these genes. [less ▲]

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See detailModulation of steroid-dependent male sexual behavior and neural gene expression: A role for steroid receptor co-activators
Charlier, Thierry ULg; Ball, Gregory F; Balthazart, Jacques ULg

in Trabajos del Instituto Cajal (2005), 80

One of the best-characterized actions of steroids is the regulation of brain areas involved in endocrine function and in the activation of reproductive behaviors in male and female vertebrates. Progress ... [more ▼]

One of the best-characterized actions of steroids is the regulation of brain areas involved in endocrine function and in the activation of reproductive behaviors in male and female vertebrates. Progress in the understanding of the mechanisms that control the expression of the eukaryotic genome by nuclear receptors has brought forward the importance of steroid receptor coactivators in mediating efficient gene transcription. However, little is know about the specific physiological requirements of these coactivators in vivo. In Japanese quail, testosterone treatment of castrated males restores the full copulatory behavior and increases the volume of the sexually dimorphic medial preoptic nucleus (POM) to the level observed in intact males [1]. Testosterone also affects a number of sexually dimorphic neurochemical characteristics such as the vasotocineric innervation of the septum and meadial preoptic nucleus [2]. The quail therefore provides an excellent model to study steroid-dependent sexual behavior and the associated neuroplasticity and should provide insights into the modulation of steroid action by steroid receptor coactivators. The present studies were focused on the steroid receptor co-activator-1 (SRC-1), which was already shown to be involved in the process of sexual differentiation of brain and behavior in rats [3]. We first amplified by RT-PCR from quail brains a 3,411bp fragment highly homologous with the chicken (94.5%) and mammalian (70%) SRC-1 and designed digoxigenin-labeled oligonucleotides for in situ hybridization. A broad distribution of SRC-1 transcripts was observed throughout the male quail brain. A particularly dense coactivator expression was observed in limbic (e.g. POM, nucleus striae terminalis) and mesencephalic (e.g. substantia grisea centralis) nuclei associated with the control of male sexual behavior [4]. Because male and female quail exhibit a very pronounced sexual dimorphism in the steroid-dependent mechanisms that activate male-typical copulatory behavior, we investigated the potential role of SRC-1 in the sexually differentiated responses to steroids by quantifiying the SRC-1 mRNA by real time quantitative polymerase chain reaction (qPCR) and the corresponding protein by western blot (WB). Contrary to previous results, which had identified a higher SRC-1 mRNA expression in the POM of males compared to females [4], we found in two separate experiments that sexually mature females had higher concentrations of SRC-1 in the preoptic area-hypothalamus (HPOA) compared to males. Additional studies should be carried out to identify the origins of this discrepancy but seasonality and time of the day when brains were collected are potentially involved. We also quantified the SRC-1 mRNA and protein in the preoptic area-hypothalamus (HPOA) of castrated males treated or not with testosterone. SRC-1 mRNA was increased by testosterone in two independent experiments but not in a third one. This difference is likely due to the differential manipulations of the birds during these experiments. Birds had been repeatedly handled to test their sexual behavior in the first experiment and we showed that stress tends to decrease the coactivator expression in the male HPOA. This interpretation is strengthened by recent work in rats indicating that stress regulates SRC-1 expression in hypothalamus and hippocampus [5]. More surprisingly, we found a significant correlation between the expression of SRC-1 and the time of the day when birds were killed in the optic lobes, hippocampus and hindbrain. The expression of SRC-1 in the optic lobes increased throughout the day, independently of sex, testosterone treatment or stress. In the hippocampus and hindbrain, the coactivator concentration varied in opposite directions during the morning and afternoon and reached respectively its lowest or highest concentration around the middle of the day, here again independently of sex, stress and hormonal treatment. Together, these data support the idea that SRC-1 is not constitutively expressed but regulated by steroids, stress and possibly other unidentified factors. Differential controls also appear to take place in specific brain nuclei and these differential controls should be further analyzed by immunohistochemistry and in situ hybridization. A second part of our work was dedicated to the study of the physiological significance of SRC-1 whith the use of daily intra-cerebroventricular injections of modified antisense (AS) oligonucleotides (Locked nucleic acid LNA) to disrupt SRC-1 expression in the POM. AS injections significantly reduced the expression of male copulatory behavior in response to exogenous testosterone compared to control animals (Ctrl group) that received the vehicle alone or scrambled (SC) oligonucleotides. Moreover, sexual behavior was restored and even enhanced within 48 hours after interruption of AS injection (ASSC group). Western blot analysis confirmed the decrease of SRC-1 expression in AS animals and demonstrated an over-expression of the coactivator in ASSC animals. The effects of SRC-1 knock down on behavior was related to a reduced POM volume defined by Nissl-staining and aromatase immunohistochemistry. The aromatase index, indicative of the relative amount of aromatase in the POM as well as the vasotocinergic innervation of this nucleus were higher in the Ctrl group. Taken together, these findings indicate that SRC-1 functions as a critical regulatory molecule in the brain to modulate steroid-dependent gene transcription and behavior. The study of the modulation of nuclear receptors activity by different co-regulatory proteins is still in its infancy. Abnormal co-activator expression or function is currently being linked to some endocrine/neurological disorders in humans and it is thus critical to understand how co-activator expression and function are controlled in the developing as well as in the adult brain. [less ▲]

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See detailTestosterone rapidly increases the volume of the medial preoptic nucleus in male Japanese quail
Charlier, Thierry ULg; Ball, Gregory F.; Balthazart, Jacques ULg

Poster (2005)

In many vertebrate species, testosterone (T) influences the volume and cellular characteristics of a variety steroid-dependent nuclei, including the medial preoptic nucleus (POM) of male Japanese quail ... [more ▼]

In many vertebrate species, testosterone (T) influences the volume and cellular characteristics of a variety steroid-dependent nuclei, including the medial preoptic nucleus (POM) of male Japanese quail. The quail POM is a key nucleus in the control of male sexual behavior and exhibits a sex difference (larger in males than in females). In castrated quail, the POM volume is markedly increased by T but previous studies always assessed this effect after a period of 8-14 days and its specific time-course is unknown. We recently reported that antisense treatments suppressing steroid receptor coactivator-1 expression block T effects on POM volume but when treatment was discontinued, a significant increase of POM size occurred within two days. We therefore asked whether this rapid neuroanatomical change was specifically linked to the SCR-1 modulation or reflected the normal rate of T-induced effects. We collected brains from castrated male quail after 1, 2, 8 and 15 days of T treatment (CX+T) while in untreated castrates (CX) brains were collected after 1 or 15 days. The POM volume defined by Nissl staining increased in a time-dependent fashion in CX+T to reach a 40% increase after 15 days while no change was observed in CX. An increase in the average POM volume was detected on day 1 (13%) and this increase was statistically significant (25%) after only 2 days of exposure to T. No volume change was observed in the steroid-insensitive nucleus rotundus. The activation of male sexual behavior was positively correlated with the increase in POM volume. Because new neurons are not incorporated in the adult avian hypothalamus, these rapid volumetric changes must reflect increases in soma size, neuropile or extracellular space. The mechanisms underlying this unexpectedly rapid neural plasticity are currently under study, focusing in particular on the potential modifications of the steroid sensitive aromatase expressing cells. [less ▲]

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See detailModulation of steroid-dependent male sexual behavior and neural gene expression: a role for steroid receptor co-activators
Charlier, Thierry ULg; Ball, Gregory F.; Balthazart, Jacques ULg

in Dawson, Alister; Sharp, Peter J. (Eds.) Functional anvian endocrinology (2005)

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See detailModulation of hormonal signaling in the brain by steroid receptor coactivators.
Charlier, Thierry ULg; Balthazart, Jacques ULg

in Reviews in the Neurosciences (2005), 16(4), 339-57

Nuclear receptors, such as estrogen, glucocorticoid or thyroid hormone receptors, have been shown to play a critical role in brain development and physiology. The activity of these receptors is modulated ... [more ▼]

Nuclear receptors, such as estrogen, glucocorticoid or thyroid hormone receptors, have been shown to play a critical role in brain development and physiology. The activity of these receptors is modulated by the interaction with several proteins and, in particular, coactivators are required to enhance their transcriptional activity. The steroid receptor coactivators (SRC-1, -2 and -3) are currently the best characterized coactivators and we review here the current knowledge on the distribution and function of these proteins in the brain. Knock-out models and antisense techniques have demonstrated the requirement for SRC-1 and -2 in the brain, focusing mainly on steroid and thyroid hormone-dependent development and behavior. The precise function of SRC-3 in the brain is currently unknown but its presence throughout the brain suggests an important function. Although the molecular biology of SRCs is relatively well known, the in vivo control of their expression, post-translational modifications and time- and cell-specific interactions with the different nuclear receptors remain elusive. A complete understanding of hormone action on brain and behavior will not be attained until a better knowledge of coactivator physiology is achieved. [less ▲]

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See detailAromatase inhibition blocks the expression of sexually-motivated cloacal gland movements in male quail
Taziaux, Mélanie ULg; Cornil, Charlotte ULg; Balthazart, Jacques ULg

in Behavioural Processes (2004), 67(3), 461-469

In Japanese quail (Coturnix japonica), activation of appetitive and consummatory aspects of male sexual behavior requires aromatization of testosterone (T) into estrogens. Appetitive male sexual behavior ... [more ▼]

In Japanese quail (Coturnix japonica), activation of appetitive and consummatory aspects of male sexual behavior requires aromatization of testosterone (T) into estrogens. Appetitive male sexual behavior (ASB) is usually assessed with the use of a learned social proximity procedure. In the present experiment, we investigated the role of estrogens in the activation of an another index of ASB. the female-induced activation of rhythmic cloacal sphincter movements (RCSMs) that are produced in reaction to the visual presentation of a female. Consummatory sexual behavior (CSB) was also assessed by the frequency and latency of copulatory behaviors. Castrated male quail were treated with Silastic implants filled with T in association with chronic injections of the aromatase inhibitor Vorozole(TM) (R83842; 1 mg/kg twice a day; CX + T + VOR group). Control birds were implanted with T capsules only (CX + T group). CSB was almost completely blocked by injections of the aromatase inhibitor. The RCSM frequency decreased progressively in the CX + T + VOR group by comparison with the CX + T group and was therefore significantly reduced at the end of the experiment. These results demonstrate that the frequency of RCSM, a second measure of ASB is, like the social proximity response and CSB, blocked by inhibition of estrogen production. It was shown previously that lesions of the preoptic area inhibit both aspects of the appetitive sexual behavior (proximity response and RCSM). It is therefore, likely that both responses are controlled, like copulation, by aromatase-containing neurons of the preoptic area. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

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See detailPreoptic aromatase modulates male sexual behavior: slow and fast mechanisms of action
Balthazart, Jacques ULg; Baillien, M.; Cornil, Charlotte ULg et al

in Physiology & Behavior (2004), 83(2), 247-270

In many species, copulatory behavior and appetitive (anticipatory/motivational) aspects of male sexual behavior are activated by the action in the preoptic area of estrogens locally produced by ... [more ▼]

In many species, copulatory behavior and appetitive (anticipatory/motivational) aspects of male sexual behavior are activated by the action in the preoptic area of estrogens locally produced by testosterone aromatization. Estrogens bind to intracellular receptors, which then act as transcription factors to activate the behavior. Accordingly, changes in aromatase activity (AA) result from slow steroid-induced modifications of enzyme transcription. More recently, rapid nongenomic effects of estrogens have been described and evidence has accumulated indicating that AA can be modulated by rapid (minutes to hour) nongenomic mechanisms in addition to the slower transcriptional changes. Hypothalamic AA is rapidly down-regulated in conditions that enhance protein phosphorylation, in particular, increases in the intracellular calcium concentration, such as those triggered by neurotransmitter (e.g., glutamate) activity. Fast changes in brain estrogens can thus be caused by aromatase phosphorylation as a result of changes in neurotransmission. In parallel, recent studies demonstrate that the pharmacological blockade of AA by specific inhibitors rapidly (within 15-45 min) down-regulates motivational and consummatory aspects of male sexual behavior in quail while injections of estradiol can rapidly increase the expression of copulatory behavior. These data collectively support an emerging concept in neuroendocrinology, namely that estrogen, locally produced in the brain, regulates male sexual behavior via a combination of genomic and nongenomic mechanisms. Rapid and slower changes of brain AA match well with these two modes of estrogen action and provide temporal variations in the estrogen's bioavailability that can support the entire range of established effects for this steroid. (C) 2004 Elsevier Inc. All rights reserved. [less ▲]

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See detailHormonal regulation of brain circuits mediating male sexual behavior in birds
Ball, G. F.; Balthazart, Jacques ULg

in Physiology & Behavior (2004), 83(2), 329-346

Male sexual behavior in both field and laboratory settings has been studied in birds since the 19th century. Birds are valuable for the investigation of the neuroendocrine mechanisms of sexual behavior ... [more ▼]

Male sexual behavior in both field and laboratory settings has been studied in birds since the 19th century. Birds are valuable for the investigation of the neuroendocrine mechanisms of sexual behavior, because their behavior can be studied in the context of a large amount of field data, well-defined neural circuits related to reproductive behavior have been described, and the avian neuroendocrine system exhibits many examples of marked plasticity. As is the case in other taxa, male sexual behavior in birds can be usefully divided into an appetitive phase consisting of variable behaviors (typically searching and courtship) that allow an individual to converge on a functional outcome, copulation (consummatory phase). Based primarily on experimental studies in ring doves and Japanese quail, it has been shown that testosterone of gonadal origin plays an important role in the activation of both of these aspects of male sexual behavior. Furthermore, the conversion of androgens, such as testosterone, in the brain to estrogens, such as 17beta-estradiol, is essential for the full expression of male-typical behaviors. The localization of sex steroid receptors and the enzyme aromatase in the brain, along with lesion, hormone implant and immediate early gene expression studies, has identified many neural sites related to the control of male behavior. The preoptic area (POA) is a key site for the integration of sensory inputs and the initiation of motor outputs. Furthermore, prominent connections between the POA and the periaqueductal gray (PAG) form a node that is regulated by steroid hormones, receive sensory inputs and send efferent projections to the brainstem and spinal cord that activate male sexual behaviors. The sensory inputs regulating avian male sexual responses, in contrast to most mammalian species, are primarily visual and auditory, so a future challenge will be to identify how these senses impinge on the POA-PAG circuit. Similarly, most avian species do not have an intromittent organ, so the projections from the POA-PAG to the brainstem and spinal cord that control sexual reflexes will be of particular interest to contrast with the well characterized rodent system. With this knowledge, general principles about the organization of male sexual circuits can be elucidated, and comparative studies relating known species variation in avian male sexual behaviors to variation in neural systems can be pursued. (C) 2004 Elsevier Inc. All rights reserved. [less ▲]

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See detailThe effects of aromatase inhibition on testosterone-dependent conditioned rhythmic cloacal sphincter movements in male Japanese quail
Cornil, Charlotte ULg; Holloway, K. S.; Taziaux, Mélanie ULg et al

in Physiology & Behavior (2004), 83(1), 99-105

Male Japanese quail produce a foam that, along with semen, is transferred to the quail hen during copulation. This foam has been reported to increase fertility, prolong sperm motility, and enhance sperm ... [more ▼]

Male Japanese quail produce a foam that, along with semen, is transferred to the quail hen during copulation. This foam has been reported to increase fertility, prolong sperm motility, and enhance sperm competition. Action of the cloacal sphincter muscles in response to visual exposure to a female produces the foam. The rhythmic cloacal sphincter movements (RCSM) responsible for foam production in male quail is elicited by a conditioned stimulus (CS) previously paired with access to a quail hen. These conditioned RCSM are testosterone-dependent. The present experiment was conducted to explore whether, as is the case with most other testosterone-dependent male sexual behaviors in the quail, conditioned RCSM are mediated by the aromatization of testosterone. Castrated, testosterone-treated male quail were presented with paired presentations of an arbitrary focal CS and visual access to a female. Once conditioned RCSM had developed, subjects received twice daily injections of the aromatase inhibitor Vorozole(TM) (R083842) during a series of extinction test presentations of the CS. Injections of Vorozole(TM) significantly decreased the number of RCSM elicited by a sexual CS. This decrease was specific to sexual RCSM; cloacal sphincter movements that occurred following defecation were not affected by Vorozole. Conditioned sexual RCSM are therefore mediated by the aromatization of testosterone, most likely due to effects on central aromatase activity related to sexual motivation. (C) 2004 Elsevier Inc. All rights reserved. [less ▲]

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See detailRapid regulation of pain by estrogens synthesized in spinal dorsal horn neurons
Evrard, H. C.; Balthazart, Jacques ULg

in Journal of Neuroscience (2004), 24(33), 7225-7229

In addition to exerting genomic actions via nuclear receptors within hours to days, estrogens also regulate neuronal activity much faster (within seconds) by activating neuronal membrane receptors coupled ... [more ▼]

In addition to exerting genomic actions via nuclear receptors within hours to days, estrogens also regulate neuronal activity much faster (within seconds) by activating neuronal membrane receptors coupled to intracellular second-messenger pathways. To date, the origin of estrogens inducing rapid effects in the brain remains unclear, although it is often ascribed to the gonads. We report here that an acute blockade of the endogenous synthesis of estrogens in the quail spinal dorsal horn markedly reduced, within 1 min, the behavioral responsiveness to a thermal painful stimulus. Similar rapid effects in the opposite direction were induced by estradiol. This finding identifies a new paracrine and nongenomic mechanism for the regulation of pain by estrogens. Such regulation was assumed previously to result only from slow genomic actions of estrogens arising from the ovaries. Also, quite importantly, this finding suggests that the numerous rapid nongenomic effects of estrogens in the CNS could depend on their immediate local production by the enzyme aromatase, independently from the gonads. [less ▲]

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See detailCatecholaminergic inputs to aromatase cells in the canary auditory forebrain
Appeltants, D.; Ball, G. F.; Balthazart, Jacques ULg

in Neuroreport (2004), 15(11), 1727-1730

The caudomedial nidopallium in songbirds is a specialized forebrain auditory region involved in the processing of species-typical vocalizations. It receives a prominent catecholaminergic projection with ... [more ▼]

The caudomedial nidopallium in songbirds is a specialized forebrain auditory region involved in the processing of species-typical vocalizations. It receives a prominent catecholaminergic projection with many fibers forming basket-like structures around non-immunoreactive cells. We investigated in male canaries the anatomical relationship between tyrosine hydroxylase and cells immunoreactive for the steroid metabolizing enzyme, aromatase, in the caudomedial nidopallium using double-label immunocytochemistry. Fibers immunoreactive for tyrosine hydroxylase established numerous close contacts with aromatase-immunoreactive cells and often encircled these cells to form basket-like structures. Aromatase containing cells in the caudomedial nidopallium are therefore a major target of catecholaminergic inputs in canary. Interactions between catecholaminergic systems and aromatase in the caudomedial nidopallium may provide one mechanism for the regulation of estrogens involved in song perception and memorization. [less ▲]

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See detailOestrogen-deficient female aromatase knockout (ArKO) mice exhibit 'depressive-like' symptomatology
Dalla, C.; Antoniou, K.; Papadopoulou-Daifoti, Z. et al

in European Journal of Neuroscience (2004), 20(1), 217-228

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by ... [more ▼]

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression. [less ▲]

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See detailThe roles of testosterone and singing in the regulation of seasonal neuroplasticity in songbirds
Sartor, Jennifer J.; Balthazart, Jacques ULg; Riters, L. V. et al

in Hormones & Behavior (2004, June), 46(1), 121

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See detailAssessment of olfactory function in male and female aromatase knockout (ArKO) mice
Pierman, S.; Douhard, Quentin ULg; Balthazart, Jacques ULg et al

in Hormones & Behavior (2004, June), 46(1), 99

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