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G C Panzica

Publications and source records attributed to G C Panzica.

At least 19 recordsLinked to original sources

Neuroactive steroids: old players in a new game.

It is now clear that the study of the effects exerted by steroids on the nervous system may be considered as one of the most interesting and promising topics for biomedical research. Indeed, new effects, mechanisms of action and targets are becoming more and more evident suggesting that steroids are not only important key regulators of nervous system function but they may also represent a new therapeutic tool to combat certain diseases of the nervous system. The present review summarizes recent observations on this topic indicating that while the concept of the nervous system as a target for steroid hormones has been appreciated for decades, a promising new era for the study of these molecules and their actions in the nervous system has been initiated in the last few years.

Animals↗

Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints.

Vasopressin neurons in the bed nucleus of the stria terminalis and amygdala and vasotocin neurons in homologous areas in non-mammalian vertebrates show some of the most consistently found neural sex differences, with males having more cells and denser projections than females. These projections have been implicated in social and reproductive behaviors but also in autonomic functions. The sex differences in these projections may cause as well as prevent sex differences in these functions. This paper discusses the anatomy, steroid dependency, and sexual differentiation of these neurons. Although the final steps in sexual differentiation of vasopressin/vasotocin expression may be similar across vertebrate species, what triggers differentiation may vary dramatically. For example, during development, estrogen masculinizes vasopressin expression in rats but feminizes its counterpart in Japanese quail. Apparently, nature consistently finds a way of maintaining sex differences in vasopressin and vasotocin pathways, suggesting that the function of these differences is important enough that it was conserved during evolution.

Androgens↗

Effects of gonadal hormones on central nitric oxide producing systems.

Nitric oxide-containing neurons are widely distributed within the CNS, including regions involved in the control of reproduction and sexual behavior. The expression of neuronal nitric oxide synthase is influenced by testosterone in male rat, and by estrogens in female. Moreover, nitric oxide synthase may co-localize with gonadal hormones' receptors. Gonadal hormones may influence nitric oxide synthase expression in adulthood as well as during the development. In fact, in mice knockout for estrogen receptor alpha, the nitric oxide synthase-expressing population is deeply reduced in specific regions. In physiological conditions, the female in mammalian species is exposed to short-term changes of gonadal hormones levels (estrous cycle). Our recent studies, performed in the rat vomeronasal system and in mouse hypothalamic and limbic systems reveal that, in rodents, the expression of nitric oxide synthase-producing elements within regions relevant for the control of sexual behavior is under the control of gonadal hormones. The expression of nitric oxide synthase may vary according to the rapid variations of hormonal levels that take place during the estrous cycle. This seems in accordance with the hypothesis that gonadal hormone activation of nitric oxide-cyclic guanosine-monophosphate pathway is important for lordosis behavior, as well as that this system is activated during mating behavior. Finally, comparative data available for other vertebrates suggest that class-specific and species-specific differences occur in the nitric oxide synthase system of hypothalamus and limbic structures. Therefore, particular caution is needed to generalize data obtained from studies in rodents.

Androgens↗

Introduction: neurobiological impact of environmental estrogens.

This paper provides an introduction to a special issue dedicated to the action of environmental estrogens on neural circuits and behavior. The problem of endocrine disrupting chemicals (EDCs), i.e. chemicals that have the capacity to interfere with the endocrine system, has gained increasing attention as it has become clear that these environmental contaminants may be active in humans, as well as in wildlife and domestic animal species. The majority of the early investigations were aimed at the discovery of the toxicological effects of the EDCs, but biomedical observations were among some of the first indications that estrogenic compounds may exert deleterious effects, even some time after exposure. The data derived from women exposed prenatally to diethylstilbesterol provided powerful evidence for long-term effects and endocrine disruption associated with selected compounds. The examination of wild animal populations exposed to industrial chemicals showed that the chemical exposure, though nonlethal, left the individual impaired or even incapable of reproducing. Among the multiple targets of the action of EDCs, several researches performed in recent years have investigated subtle modifications of the animal behaviors (reproductive, aggressive) that are likely to be related to alterations of specific neural pathways. We have, therefore, focused here on the behavioral studies as one of the more powerful tools to investigate EDCs effects on specific neural circuits.

Animals↗

Region-specific testosterone modulation of the vasotocin-immunoreactive system in male dark-eyed junco, Junco hyemalis.

The nonapeptide vasotocin (VT) is the avian equivalent of the mammalian antidiuretic hormone vasopressin and is believed to control aggressive and reproductive behaviors. Brain VT distribution has been described in several domesticated avian species. We previously demonstrated that VT distribution in the brain of a free-ranging male passerine, the dark-eyed Junco, Junco hyemalis, resembles that in domesticated birds. A preliminary study also suggested that the VT-immunoreactive (VT-ir) system of juncos is regulated by testosterone (T), as is the case of galliforms. To test this hypothesis, we investigated the effects of castration and T replacement on brain VT-ir innervation in adult male juncos. Castration reduced VT-ir innervation in the lateral septum (SL), the medial preoptic nucleus, the nucleus of the stria terminalis and the intercollicularis nucleus. These effects of castration were largely reversed by T treatment at high physiological doses, but significantly so only for the SL. Given the demonstrated behavioral role of the above VT-ir-containing brain regions, the results suggest that these regions may be sites of action of VT on reproductive behaviors.

Animals↗

Expression of neuropeptides and growth-associated protein 43 (GAP-43) in cutaneous and mucosal nerve structures of the adult rat lower lip after mental nerve section.

The reinnervation of the adult rat lower lip has been investigated after unilateral section of the mental nerve. Rats were sacrificed at 4, 7, 9, 14, 30, and 90 days after the operation. A further group of animals with section of the mental nerve and block of the alveolar nerve regeneration, was sacrificed at 14 days. Specimens were processed for immunocytochemistry with antibodies against PGP 9.5, GAP-43 or neuropeptides (CGRP, SP and VIP). Four days after nerve section, axonal degeneration seems evident in the mental nerve branches and inside skin and mucosa. GAP-43 immunoreactivity is intense in the mental nerve 7 days after nerve section and it reaches its maximal expression and distribution in peripheral nerve fibres at 14 days. At 30 days, the decline in its expression is associated with the increase of PGP9.5-, SP-, and CGRP immunopositivity. VIP is observed only in perivascular fibres at all times observed. Present results suggest that, after sensory denervation of the rat lip, nerve fibres in skin and mucosa remain at lower density than normal. The different time courses in the expression of neuropeptides and GAP-43 suggest a possible early involvement of GAP-43 in peripheral nerve regeneration.

Animals↗

Changes in the arginine-vasopressin immunoreactive systems in male mice lacking a functional aromatase gene.

In male rodents, the arginine-vasopressin-immunoreactive (AVP-ir) neurones of the bed nucleus of the stria terminalis (BNST) and medial amygdala are controlled by plasma testosterone levels (decreased after castration and restored by exogenous testosterone). AVP transcription in these nuclei is increased in adulthood by a synergistic action of the androgenic and oestrogenic metabolites of testosterone and, accordingly, androgen and oestrogen receptors are present in both BNST and medial amygdala. We used knockout mice lacking a functional aromatase enzyme (ArKO) to investigate the effects of a chronic depletion of oestrogens on the sexually dimorphic AVP system. Wild-type (WT) and ArKO male mice were perfused 48 h after an i.c.v. colchicine injection and brain sections were then processed for AVP immunocytochemistry. A prominent decrease (but not a complete suppression) of AVP-ir structures was observed in the BNST and medial amygdala of ArKO mice by comparison with the WT. Similarly, AVP-ir fibres were reduced in the lateral septum of ArKO mice and but not in the medial preoptic area, a region where the AVP system is not sexually dimorphic in rats. No change was detected in the supraoptic and suprachiasmatic nuclei. However, a decrease in AVP-ir cell numbers was however, detected in one subregion of the paraventricular nucleus. These data support the hypothesis that the steroid-sensitive sexually dimorphic AVP system of the mouse forebrain is mainly under the control of aromatized metabolites of testosterone.

Animals↗

Sexually dimorphic neurogenesis is topographically matched with the anterior accessory olfactory bulb of the adult rat.

The accessory olfactory bulb (AOB) is a sexually dimorphic structure of the vomeronasal system, which plays a role in the control of sexual behaviors. In adult rats, we have demonstrated previously that the migrating neuroblasts of the subependymal layer (SEL) directed to the main olfactory bulb (MOB) also reach the AOB. To tackle the relation between sexual dimorphism and targeted cell migration, we quantified the neo-neurogenesis in the AOB of adult rats of both sexes. Our results confirm a morphological sexual dimorphism in the AOB granular layer volumes. We showed that the number of newly generated cells reaching the AOB in both sexes was considerable, even if lower than those directed to the MOB. Moreover, we demonstrated that the rate of neurogenesis in the anterior AOB of the two sexes was significantly different.

Age Factors↗

Estradiol mediates effects of testosterone on vasotocin immunoreactivity in the adult quail brain.

In adult male quail, the activation of sexual behavior by testosterone (T) is mediated at the cellular level by the interaction of T metabolites with intracellular steroid receptors. In particular, the aromatization of T into an estrogen plays a key limiting role. Nonaromatizable androgens such 5alpha-dihydrotestosterone (DHT) synergize with estradiol (E2) to activate the behavior. Given that the density of vasotocin (VT) immunoreactive structures is increased by T in adult male quail and that VT injections affect male behavior, we wondered whether the expression of VT is also affected by T metabolites such as E2 and DHT. We analyzed here, in castrated male quail, the effects of a treatment with T, E2, DHT, or E2 + DHT on sexual behavior and brain VT immunoreactivity. The restoration by T of the VT immunoreactivity in the medial preoptic nucleus, bed nucleus striae terminalis, and lateral septum of castrated male quail could be fully mimicked by a treatment with E2. The androgen DHT had absolutely no effect on the VT immunoreactivity in these conditions and, at the doses used here, DHT did not synergize with E2 to enhance the density of VT immunoreactive structures. These effects of T metabolites in the brain were not fully correlated with their effects on the activation of male copulatory behavior, suggesting that the increase in VT expression in the brain does not represent a necessary step for the activation of behavior. Although VT expression in the medial preoptic nucleus and bed nucleus striae terminalis is often tightly correlated with the expression of male copulatory behavior, VT presumably does not represent simply one step in the biochemical cascade of events that is induced by T in the brain and leads to the expression of male sexual behavior.

Animals↗

Steroid-induced plasticity in the sexually dimorphic vasotocinergic innervation of the avian brain: behavioral implications.

Vasotocin (VT, the antidiuretic hormone of birds) is synthesized by diencephalic magnocellular neurons projecting to the neurohypophysis. In addition, in male quail and in other oscine and non-oscine birds, a sexually dimorphic group of VT-immunoreactive (ir) parvocellular neurons is located in a region homologous to the mammalian nucleus of the stria terminalis, pars medialis (BSTm) and in the medial preoptic nucleus (POM). These cells are not visible in females. VT-ir fibers are present in many diencephalic and extradiencephalic locations. Quantitative morphometric analyses demonstrate that, in quail, these elements are expressed in a sexually dimorphic manner (males>females) in regions involved in the control of different aspects of reproduction: i.e., the POM (copulatory behavior), the lateral septum (secretion of gonadotropin-releasing hormone [GnRH]), the nucleus intercollicularis (control of vocalizations), and the locus coeruleus (the main noradrenergic center of the avian brain). In many of these regions, VT-ir fibers are closely related to aromatase-ir, GnRH-ir, or estrogen receptor-expressing neurons. This dimorphism has an organizational nature: administration of estradiol-benzoate to quail embryos (a treatment that abolishes male sexual behavior) results in a dramatic decrease of the VT-immunoreactivity in all sexually dimorphic regions of the male quail brain. Conversely, the inhibition of estradiol (E2) synthesis during embryonic life (a treatment that stimulates the expression of male copulatory behavior in adult testosterone (T)-treated females) results in a male-like distribution of VT-ir cells and fibers. Castration markedly decreases the immunoreactivity in both the VT-immunopositive elements of the BSTm and the innervation of the SL and POM, whereas T-replacement therapy restores the VT immunoreactivity to a level typical of intact birds. These changes reflect modifications of VT mRNA concentrations (and probably synthesis) as demonstrated by in situ hybridization and they are paralleled by similar changes in male copulatory behavior (absent in castrated male quail, fully expressed in CX+T males). The aromatization of T into estradiol (E2) also controls VT expression and, in parallel limits the activation of male sexual behavior by T. In castrated male quail, the restoration by T of the VT immunoreactivity in POM, BSTm and lateral septum could be fully mimicked by a treatment with E2, but the androgen 5alpha-dihydrotestosterone (DHT) had absolutely no effect on the VT immunoreactivity in these conditions. At the doses used in this study, DHT also did not synergize with E2 to enhance the density of VT immunoreactive structures. Systemic or i.c.v. injections of VT markedly inhibit the expression of all aspects of male sexual behavior. VT, presumably, does not simply represent one step in the biochemical cascade of events that is induced by T in the brain and leads to the expression of male sexual behavior. Androgens and estrogens presumably affect reproductive behavior both directly, by acting on steroid-sensitive neurons in the preoptic area, and indirectly, by modulating peptidergic (specifically vasotocinergic) inputs to this and other areas. The respective contribution of these two types of actions and their interaction deserves further analysis.

Animals↗

The control of preoptic aromatase activity by afferent inputs in Japanese quail.

This review summarizes current knowledge on the mechanisms that control aromatase activity in the quail preoptic area, a brain region that plays a key role in the control of reproduction. Aromatase and aromatase mRNA synthesis in the preoptic area are enhanced by testosterone and its metabolite estradiol, but estradiol receptors of the alpha subtype are not regularly colocalized with aromatase. Estradiol receptors of the beta subtype are present in the preoptic area but it is not yet known whether these receptors are colocalized with aromatase. The regulation by estrogen of aromatase activity may be, in part, trans-synaptically mediated, in a manner that is reminiscent of the ways in which steroids control the activity of gonadotropic hormone releasing hormone neurons. Aromatase-immunoreactive neurons are surrounded by dense networks of vasotocin-immunoreactive and tyrosine hydroxylase-immunoreactive fibers and punctate structures. These inputs are in part steroid-sensitive and could therefore mediate the effects of steroids on aromatase activity. In vivo pharmacological experiments indicate that catecholaminergic depletions significantly affect aromatase activity presumably by modulating aromatase transcription. In addition, in vitro studies on brain homogenates or on preoptic-hypothalamic explants show that aromatase activity can be rapidly modulated by a variety of dopaminergic compounds. These effects do not appear to be mediated by the membrane dopamine receptors and could involve changes in the phosphorylation state of the enzyme. Together, these results provide converging evidence for a direct control of aromatase activity by catecholamines consistent with the anatomical data indicating the presence of a catecholaminergic innervation of aromatase cells. These dopamine-induced changes in aromatase activity are observed after several hours or days and presumably result from changes in aromatase transcription but rapid non-genomic controls have also been identified. The potential significance of these processes for the physiology of reproduction is critically evaluated.

Afferent Pathways↗

Increased expression of the neuropeptide Y receptor Y(1) gene in the medial amygdala of transgenic mice induced by long-term treatment with progesterone or allopregnanolone.

The neurosteroid allopregnanolone, a reduced metabolite of progesterone, induces anxiolytic effects by enhancing GABA(A) receptor function. Neuropeptide Y (NPY) and GABA are thought to interact functionally in the amygdala, and this interaction may be important in the regulation of anxiety. By using Y(1)R/LacZ transgenic mice, which harbour a fusion construct comprising the promoter of the mouse gene for the Y(1) receptor for NPY linked to the lacZ gene, we previously showed that long-term treatment with benzodiazepine receptor ligands modulates Y(1) receptor gene expression in the medial amygdala. We have now investigated the effects of prolonged treatment with progesterone or allopregnanolone on Y(1)R/LacZ transgene expression, as determined by quantitative histochemical analysis of beta-galactosidase activity. Progesterone increased both the cerebrocortical concentration of allopregnanolone and beta-galactosidase expression in the medial amygdala. Finasteride, a 5alpha-reductase inhibitor, prevented both of these effects. Long-term administration of allopregnanolone also increased both the cortical concentration of this neurosteroid and transgene expression in the medial amygdala. Treatment with neither progesterone nor allopregnanolone affected beta-galactosidase activity in the medial habenula. These data suggest that allopregnanolone regulates Y(1) receptor gene expression through modulation of GABA(A) receptor function, and they provide further support for a functional interaction between GABA and neuropeptide Y in the amygdala.

Amygdala↗

Cutaneous innervation in hereditary sensory and autonomic neuropathy type IV.

The authors investigated immunocytochemically the innervation of a skin biopsy in a rare case of hereditary sensory and autonomic neuropathy type IV. A few protein gene product 9.5-, growth-associated protein 43-, calcitonin gene-related peptide-, and substance P-immunoreactive nerve fibers were observed in the deeper regions of the dermis. Neuropeptide Y-, nitric oxide-, and vasoactive intestinal polypeptide-immunoreactive fibers were completely absent. Their observations support the hypothesis that the sensory and autonomic defects reported in hereditary sensory and autonomic neuropathy are based on profound developmental alterations of the peripheral nervous system.

Calcitonin Gene-Related Peptide↗

Effects of testosterone on the synaptology of the medial preoptic nucleus of male Japanese quail.

The medial preoptic nucleus (POM) of male Japanese quail is a sexually dimorphic testosterone-dependent structure that plays a key role in the activation of male sexual behavior. Both the total volume of the nucleus and the size of the dorsolateral neurons are decreased in gonadectomized males. Immunocytochemical studies have revealed a complex pattern of innervation: immunopositive fibers for several neuropeptides and neurotransmitters have been detected in the POM; some of them (e.g. vasotocin-immunoreactive fibers) are sexually dimorphic and testosterone-dependent To understand the anatomical bases of these testosterone-dependent neurochemical changes, we performed an ultrastructural study of the POM neuropil in intact sexually mature, gonadectomized, or testosterone-treated gonadectomized males. A complex synaptic organization of the POM neuropil was observed in intact male quail reflecting the heterogeneity of the neurotransmitters and neuropeptides present in this nucleus. Changes in this organization were observed after the endocrine manipulations. The number of axosomatic synapses per cell body decreased after gonadectomy and was restored to the level observed in the intact group after the administration of testosterone. By contrast, no significant change was observed in the density of axodendritic and axospinal synapses after hormonal manipulations which suggests that the total number of synapses in the nucleus should be affected by testosterone (constant density in a changing total volume). The cross-sectional area of synaptic boutons was also decreased by castration and restored to intact level by testosterone. The action of testosterone on the activation of male copulatory behavior in gonadectomized birds is hence paralleled by an extensive rearrangement of neuropil in the POM.

Analysis of Variance↗

Central vasotocin-immunoreactive system in a male passerine bird (Junco hyemalis).

Previous investigations have identified regions of the avian brain that contain immunoreactive vasotocinergic (VT-ir) cell bodies and fibers. These studies exclusively used domesticated species, and the relevance of the findings for free-living birds has not been established. The present study used immunocytochemistry to determine the neuroanatomical distribution of the VT-ir system in the brain of a well-studied male passerine bird (dark-eyed junco, Junco hyemalis) obtained from a natural population in interior Alaska (65 degrees N, 147 degrees W). VT-ir cell bodies were observed in several brain regions (paraventricular and supraoptic nuclei, nucleus of the stria terminalis), where they have been described in other oscine species. VT-ir fibers were widespread in many brain regions and were especially abundant in the medial preoptic nucleus, the basal region of the septum, and the hypothalamic-neurohypophyseal tract. Fibers were also present in brain regions that are involved in the control of vocal behavior including the ventromedial capsular region of the nucleus robustus archistriatalis and the dorsomedial portion of the mesencephalic nucleus intercollicularis. The widespread brain distribution of VT-ir cell bodies and fibers in juncos generally resembles that of domestic birds and suggests a role for this neuropeptide in the control of reproductive behavior and physiology.

Animals↗

Immunocytochemical evidence of plasticity in the nervous structures of the rat lower lip.

In this immunocytochemical study we investigated the distribution of nervous structures in the lower lip of adult rats. The region is characterized by a rich cutaneous and mucosal sensory innervation originating from terminal branches of the trigeminal system. Lower lip innervation was investigated by detection of the general neuronal marker protein gene product 9.5 (PGP 9.5) and the growth-associated protein 43 (GAP-43), a neurochemical marker of neuronal plasticity. The entire neural network of both cutaneous and mucosal aspects was stained by the antibody to PGP 9.5. In particular, nerve fibers were observed in the submucosal and the subepithelial plexuses. Thin immunoreactive fibers were observed within the epithelial layers ending as free fibers or as fibers associated with immunopositive Merkel cells. Well-identified anatomical structures receiving sensory or autonomic innervation were also surrounded by PGP 9.5-ir nerve fibers, in particular, hair follicles, vibrissae, glands, and blood vessels. GAP-43-immunostained nerve fibers were observed in all these structures; however, they were generally less numerous than the PGP 9.5-immunoreactive elements. An equal amount of PGP 9.5 and GAP-43 immunoreactivity occurred, in contrast, in the subepidermal and the submucosal plexuses, or in the epidermis and the mucosal epithelium. The present results show that GAP-43 is normally expressed in the mature trigeminal sensory system of the rat. Skin and oral mucosa are characterized by continuous remodeling that may also involve the sensory nervous apparatus. Continuous neural remodeling, regeneration and sprouting may be the reason for the observed expression of GAP-43.

Animals↗

Gonadal steroid-dependent neuronal circuitries in avian limbic and preoptic regions.

In the avian limbic and preoptic region, the sexually dimorphic medial preoptic nucleus and nucleus of the stria terminalis are characterized by the presence of a testosterone-dependent aromatase-immunoreactive neuronal population. In situ hybridization studies confirmed that testosterone is modulating the expression of aromatase gene. Both nuclei are also characterized by a sexually dimorphic, testosterone-dependent vasotocin system. Immunocytochemical and in situ hybridization data, demonstrated that dimorphism and testosterone-sensitivity of this system are both dependent by an embryonic organizational effect of the estradiol. Intracerebroventricularly injected vasotocin, has a profound inhibitory effect on the male sexual behaviour, and immunocytochemical investigations revealed close associations among vasotocin fibres and aromatase cell bodies. These data suggest that this neuropeptidergic system could have a key role in the circuitries controlling different aspects of male reproductive behaviour in the Japanese quail.

Animals↗