RESUMO
In the present study, we investigated the role of the androgen receptor (AR) in the nervous system in the regulation of aggressive behavior and arginine vasopressin and galanin systems by testosterone. For this purpose, we used a conditional mouse line selectively lacking AR gene in the nervous system, backcrossed onto the C57BL/6J strain. Adult males were gonadectomized and supplemented with similar amounts of testosterone. When tested on two consecutive days in the resident intruder paradigm, fewer males of the mutant group exhibited aggressive behavior compared to their control littermates. In addition, a high latency to the first offensive attack was observed for the few animals that exhibited fighting behavior. This alteration was associated with a normal anogenital chemoinvestigation of intruder males. In olfactory discrimination tasks, sexual experience enhanced preference towards female-soiled bedding rather than male-soiled bedding and estrus females rather than intact males, regardless of genotype. This indicated that the behavioral alteration induced by neural AR mutation occurs in brain areas located downstream from the olfactory bulb. Quantification of the sexually dimorphic cell populations expressing preprovasopressin and galanin mRNAs in the bed nucleus of stria terminalis (BNST) and vasopressin-neurophysin 2 and galanin immunoreactivity in the lateral septum showed no significant differences between the two genotypes. The present findings indicate that the neural AR is required in the expression of aggressive behavior but not in the sexual differentiation of AVP and galanin cell number in the BNST and fiber immunoreactivity in the lateral septum. They also suggest that AR in the nervous system could mediate activational effects of testosterone in the regulation of aggressive behavior during adulthood.
Assuntos
Arginina Vasopressina/metabolismo , Galanina/metabolismo , Receptores Androgênicos/metabolismo , Agressão/fisiologia , Animais , Imuno-Histoquímica , Hibridização In Situ , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Nervoso/metabolismo , RNA Mensageiro/genética , Receptores Androgênicos/genética , Testosterona/metabolismoRESUMO
Biomimicry is a growing field of developing environmental innovations for materials, facade systems, buildings, and urban planning. In France, we observe an extensive diversity of initiatives in biomimicry for the development of regenerative cities. These initiatives blossom in a large range of areas, from education to urban policies, to achieve a major environmental, social and economic paradigm shift. To provide a comprehensive understanding of this development at the national scale, this paper presents and discusses the diversity of the developed initiatives over the last 10 years in six main fields-education, urban policies, fundamental and applied research, design demonstrators, arts, and communication. This research is an opportunistic study based on the analysis of these initiatives enriched by the feedback of the stakeholders collected by the authors working in the field of biomimicry over the last seven years. We identify that biomimicry in France has mainly extended through individual initiatives of teachers, territorial authorities, architectural studios, or researchers rather than through the support of public policies. Putting into perspective developments in biomimicry by other countries, this cross-discipline analysis provides recommendations for the extensive development of regenerative architecture and urbanism at the national scale.
RESUMO
Biomimicry is a design framework with growing interests in sustainable architectural and urban design practice. Nevertheless, there is a significant lack of studies and knowledge regarding its practical application. In 2020, a French workgroup called Biomim'City Lab published a document identifying and describing 16 urban projects designed by French teams integrating biomimicry at various levels. Our research is an opportunistic study analyzing this data, aiming to identify trends and challenges in the French market. We analyzed the projects using a mixed-method approach, through quantitative typological analysis and qualitative narrative analysis. This sample of French projects indicates a trend of increasing interest in biomimicry on built space projects in France. Biomimicry was primarily applied at the façade/roof/soil systems, mostly using macroscopic models as ecosystems, plants, and animals. Designers declared to aim diverse objectives with the biomimetic approach; still, thermal comfort is the most recurrent in the sample. We also identified that challenges remain to foster the field application, as the lack of awareness of the urban fabric stakeholders on the topic and the gaps between research and design practice.
RESUMO
Testosterone (T) profoundly influences central sexual differentiation and functions. In the brain, T signals either directly through androgen receptor (AR) or indirectly through estrogen receptor (ER) following aromatization into E2 (17-beta-estradiol). As T, through AR, also controls peripheral male sexual differentiation, the relative contribution of central AR in T-mediated regulation of behavioral and neuroendocrine responses still remains unclear. To address this question, we generated, by using Cre-loxP technology, mice selectively lacking AR expression in the nervous system. The mutant male urogenital tract was normally developed, and mice were able to produce offspring. Nonetheless, sexual motivation and performance as well as aggressive behaviors were affected. Only a low percentage of males displayed a complete sexual behavior and offensive attacks. The latency to show masculine behaviors was increased and copulation length prolonged. Erectile activity during mating was also altered. These alterations occurred despite increased levels of T and its metabolites, and an unaffected number of ERalpha-immunoreactive cells. Olfactory preference and neuronal activation, mapped by Fos immunoreactivity, following exposure to estrus female-soiled bedding were also normal. At comparable T levels, greater differences in masculine behaviors were observed between gonadectomized control and mutant males. AR invalidation in the nervous system also disrupted the somatotropic axis since mutant males exhibited growth retardation and decreased serum levels of insulin-like growth factor I. Our findings show that central AR is required in T-induced regulation of male-typical behaviors and gonadotrope and somatotropic axes. This genetic model offers a unique opportunity in the understanding of AR's role in cerebral functions of T.
Assuntos
Sistema Nervoso/metabolismo , Sistemas Neurossecretores/fisiologia , Receptores Androgênicos/deficiência , Receptores Androgênicos/genética , Comportamento Sexual Animal/fisiologia , Animais , Cérebro/metabolismo , Cérebro/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Genéticos , Sistemas Neurossecretores/metabolismo , Gravidez , Receptores Androgênicos/metabolismoRESUMO
There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 µg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.
Assuntos
Compostos Benzidrílicos/administração & dosagem , Estrogênios não Esteroides/administração & dosagem , Rede Nervosa/efeitos dos fármacos , Fenóis/administração & dosagem , Área Pré-Óptica/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Administração Oral , Animais , Comportamento de Escolha/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Kisspeptinas/metabolismo , Masculino , Camundongos , Rede Nervosa/metabolismo , Área Pré-Óptica/metabolismo , Receptores Androgênicos/metabolismo , Olfato/efeitos dos fármacosRESUMO
Androgens including testosterone, organize the nervous system as well as masculine external and internal genitalia during the perinatal period. Androgen organization involves promotion of masculine body features, usually by acting through androgen receptors (ARs). We have recently demonstrated that the gastrin-releasing peptide (GRP) system in the lumbar spinal cord also mediates spinal centers promoting penile reflexes during male sexual behavior in rats. Testosterone may induce sexual differentiation of this spinal GRP system during development and maintain its activation in adulthood. In the present study, we examined the role of ARs in the nervous system regulating the development of the sexually dimorphic GRP system. For this purpose, we used a conditional mouse line selectively lacking the AR gene in the nervous system. AR floxed males carrying (mutants) or not (controls) the nestin-Cre transgene were castrated in adulthood and supplemented with physiological amounts of testosterone. Loss of AR expression in the nervous system resulted in a significant decrease in the number of GRP neurons compared to control littermates. Consequently, the intensity of GRP axonal projections onto the lower lumbar and upper sacral spinal cord was greater in control males than in mutant males. These results suggest that ARs expressed in the nervous system play a significant role in the development of the GRP system in the male lumbar spinal cord. The AR-deletion mutation may attenuate sexual behavior and activity of mutant males via spinal GRP system-mediated neural mechanisms.
Assuntos
Peptídeo Liberador de Gastrina/metabolismo , Neurônios/metabolismo , Receptores Androgênicos/genética , Medula Espinal/metabolismo , Animais , Castração , Contagem de Células , Região Lombossacral , Masculino , Camundongos Mutantes , Mutação , Neurônios/citologia , Receptores Androgênicos/metabolismo , Caracteres Sexuais , Medula Espinal/citologia , Testosterona/farmacologiaRESUMO
Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) and their target bulbocavernosus (BC) and levator ani (LA) muscles play a role in male copulation and fertility. Testosterone (T) induces sexual differentiation of this SNB neuromuscular system during development and maintains its activation in adulthood. In the rat, T-induced effects mostly involve the androgen receptor (AR). However, the role of central AR in T-induced effects remains to be studied with pertinent genetic models. We addressed this question by using specific motoneuron immunolabeling and retrograde tracing in mice selectively disrupted for AR in the nervous system. This work reveals that nervous system AR is not required either for T-induced development of BC-LA muscles and perinatal sparing of SNB motoneurons from atrophy or for adult sensitivity of BC-LA muscles to T. By contrast, loss of AR expression in the nervous system resulted in SNB motoneurons having smaller somata and shorter dendrites than controls. We studied the effects of adult castration and T supplementation on SNB cell morphology in control and mutant males; these experiments showed that central AR is involved in the developmental regulation of soma size and dendritic length and in the adult maintenance of soma size of SNB motoneurons. T seemed to act indirectly through BC-LA muscles to maintain dendritic length in adulthood. Our results also suggest that central AR functions may contribute to normal activity of SNB motoneurons and perineal muscles because mutant mice displayed diminished copulatory behavior and fertility.