Anna Costagliola - Academia.edu (original) (raw)
Papers by Anna Costagliola
Frontiers in Veterinary Science
Orexins A (OXA) and B (OXB) and the receptors 1 (OX1R) and 2 (OX2R) for orexins are hypothalamic ... more Orexins A (OXA) and B (OXB) and the receptors 1 (OX1R) and 2 (OX2R) for orexins are hypothalamic peptides found in several mammalian organs and participated to the control of a wide assortment of physiological and pathological functions. The distribution of OXA and OX1R has been extensively studied in the male gonad of mammals. Here, we examined the expression and localization of OXB and OX2R as well as their possible involvement in the regulation of testicular and epididymal functions, in healthy and cryptorchid dogs, employing some techniques such as immunohistochemistry, Western blotting, and real-time RT-PCR. In vitro tests were also carried out for evaluating the steroidogenic effect of OXB. OXB and OX2R were expressed in spermatocytes, spermatids, and Leydig cells in normal testis. Their localization was restricted to Sertoli and Leydig cells in cryptorchid conditions. OXB was found to be localized in all tracts of both normal and cryptorchid epididymis, whereas OX2R was found...
Animals
Animal-assisted interventions (AAI)s represent the expression of integrated medicine, according t... more Animal-assisted interventions (AAI)s represent the expression of integrated medicine, according to the One Health approach. Actually, animal-assisted therapies and animal-assisted activities are implemented in hospitals, rehabilitation centers, etc. The efficacy of AAIs is based on interspecific interactions and would be impacted by different factors, such as the characters of both the animal and the handler, a suitable selection of animal species, an appropriate animal educational protocol, the relationship between the handler and the animal, and mutual relationship among the animal, the patients, and members of the working team. AAIs produce many advantages for the patients but could expose them to zoonotic-pathogens transmission. Therefore, positive animal welfare, as preventative medicine to avoid incidents or transmission of zoonosis, is a relevant aspect with implications for human and animal health and wellbeing. This review aims to summarize the current published knowledge r...
Neuronal control of the vagina in vertebrates: A review
Acta Histochemica
Animals, 2020
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genu... more Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genus. It is 96.2% homologous to bat CoV RaTG13 and 88% homologous to two bat SARS-like coronaviruses. SARS-CoV-2 is the infectious agent responsible for the coronavirus disease (COVID-19), which was first reported in the Hubei province of Wuhan, China, at the beginning of December 2019. Human transmission from COVID-19 patients or incubation carriers occurs via coughing, sneezing, speaking, discharge from the nose, or fecal contamination. Various strains of the virus have been reported around the world, with different virulence and behavior. In addition, SARS-CoV-2 shares certain epitopes with some taxonomically related viruses, with tropism for the most common synanthropic animals. By elucidating the immunological properties of the circulating SARS-CoV-2, a partial protection due to human–animal interactions could be supposed in some situations. In addition, differential epitopes could be ...
Animal reproduction science, 2018
The steroidogenic enzyme P450 aromatase (ARO) has a key role in the conversion of testosterone (T... more The steroidogenic enzyme P450 aromatase (ARO) has a key role in the conversion of testosterone (T) into estrogens (E), expressed as 17β-estradiol. The presence and localization of this key enzyme have not been described before in the South American camelid alpaca (Vicugna pacos). In our previous studies of the expression and biological effects of orexin A (OxA) and OxB on the alpaca testis demonstrated that OxA, via its specific receptor 1 (OX1R), stimulated T synthesis. In order to extend these findings, we presently explored the presence and localization of ARO in the alpaca male gonad, and the possible correlation between ARO and the orexinergic complex. Western blotting and immunohistochemistry demonstrated the presence of ARO in tissue homogenates and its localization in the tubular and interstitial compartments of the alpaca testis, respectively. The addition of OxA to fresh testicular slices decreased the 17β-estradiol E levels. This effect was annulled by the sequential addi...
BMC veterinary research, Jan 27, 2018
Cryptorchidism is one of the most common birth disorders of the male reproductive system identifi... more Cryptorchidism is one of the most common birth disorders of the male reproductive system identified in dogs and other mammals. This condition is characterised by the absence of one (unilateral) or both (bilateral) gonads from the scrotum. The peptides orexin A (OxA) and B (OxB) were obtained by post-transcriptional proteolytic cleavage of a precursor molecule, called prepro-orexin. These substances bind two types of G-coupled receptors called receptor 1 (OX1R) and 2 (OX2R) for orexins. OX1R is specific to OxA while OX2R binds the two peptides with equal affinity. Orexins modulate a great variety of body functions, such as the reproductive mechanism. The purpose of the present research was to study the presence of OxA and its receptor 1 and their possible involvement in the canine testis under healthy and pathological conditions. This study was performed using adult male normal dogs and male dogs affected by unilateral cryptorchidism. Tissue samples were collected from testes and wer...
Acta histochemica, 2018
The peptides orexin A (OXA) and orexin B (OXB) derived from the proteolytic cleavage of a common ... more The peptides orexin A (OXA) and orexin B (OXB) derived from the proteolytic cleavage of a common precursor molecule, prepro-orexin, were originally described in the rat hypothalamus. Successively, they have been found in many other brain regions as well as in peripheral organs of mammals and other less evolved animals. The widespread localization of orexins accounts for the multiple activities that they exert in the body, including the regulation of energy homeostasis, feeding, metabolism, sleep and arousal, stress, addiction, and cardiovascular and endocrine functions. Both OXA and OXB peptides bind to two G-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R) receptor, though with different binding affinity. Altered expression/activity of orexins and their receptors has been associated with a large number of human diseases. Though at present evidence highlighted a role for orexins and cognate receptors in mammalian reproduction, their central and/or local effects on gonadal func...
Reproduction in Domestic Animals, 2017
The orexins A (OxA) and B (OxB) are two hypothalamic peptides involved in many physiological func... more The orexins A (OxA) and B (OxB) are two hypothalamic peptides involved in many physiological functions of the mammalian body. They act through the binding of two G-coupled receptors named receptor 1 (OX 1 ) and receptor 2 (OX 2 ) for orexins. The first receptor is specific for OxA, while the second binds both the substances with equal affinity. The orexins and the relative receptors have been traced by means of different techniques also at the periphery of the body and particularly in the adrenals, and in gastrointestinal and genital organs. Aim of this work was to investigate the presence of OxB and OX 2 by means of immunohistochemistry and Western blotting analysis in the testis of the South American camelid alpaca, a species primarily breed in Chile and Ecuador and recently diffused in Europe where the quality of its wool is particularly appreciated. OxB immunoreactivity (IR) was found in the tubular compartment of the testis where spermatogonia (resting), zygotene and pachytene spermatocytes, and spermatids clearly showed differently sized and shaped cytoplasmic positive structures. OX 2 -IR was found both in the interstitial and tubular compartments of the testis and particularly in Leydig cells and round and elongated spermatids. Western blotting analysis of testis lysates showed the presence of a protein band whose molecular weight corresponded to that currently assigned to OX 2 . Such findings easily translate the hypothesis that OxB and its receptor 2 play a functional role both in the interstitial and tubular compartments of the alpaca testis.
Journal of neuroscience research, Jan 18, 2017
Over the past century, a huge amount of evidence has emerged pointing to the role of the neurotra... more Over the past century, a huge amount of evidence has emerged pointing to the role of the neurotransmitter serotonin, the neuropeptides orexin A and B, and the small gaseous molecule nitric oxide (NO) (Fig. 1) as crucial regulators of both physiological functions and diseases of the central nervous system (CNS) and peripheral organs as well (Berger et al., 2009; Zhou and Zhu, 2009; Shekhar, 2012). Serotonin, orexins, and NO produced in the brain centrally regulate a great number of neural activities including synaptic plasticity, sleep-wake cycle, energy balance, food intake, hormone secretion, immune responses, cardiovascular functions, and others (Szczepanska-Sadowska et al., 2010; Hu and Zhu, 2014; Shan et al., 2015). Interestingly, these regulatory factors are even involved in the complex neurobiological phenomenon relying on trust, belief, pleasure, and reward activities such as love (Esch and Stefano, 2005). They play major roles in the control of partner preference, sexual desire, erection, copulation, ejaculation, orgasm, and sexual satiety. Serotonin, orexins, NO, and their synthetic and signaling machineries are not limited to the neural tissues and brain, but they are also expressed in peripheral tissues, where their prominent role begins from the time of the morphogenesis in utero and lasts through all of adult life. Peripheral locally produced serotonin, orexins, and NO regulate cardiovascular system physiology, bowel motility, steroidogenesis in the adrenal glands and the genital tract, urethrogenital reflex, vascular smooth muscle contractility, platelet aggregation, immunity, and many other physiological processes (F€ orstermann and Sessa, 2012; Amireault et al., 2013; Li et al., 2014). The regulatory activities of the three neuromodulators depend on the place of their release and the availability of specific receptors; thus, they may exert either stimulatory or inhibitory effects depending on the site of action. An elevated number of disorders affecting either CNS or peripheral organs including psychiatric
Expression and potential role of the peptide orexin-A in prostate cancer
Biochemical and Biophysical Research Communications, 2015
The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved... more The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved in multiple physiological processes in the central nervous system and peripheral organs. Altered expression or signaling dysregulation of orexins and their receptors have been associated with a wide range of human diseases including narcolepsy, obesity, drug addiction, and cancer. Although orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been detected in the human normal and hyperplastic prostate tissues, their expression and function in the prostate cancer (PCa) remains to be addressed. Here, we demonstrate for the first time the immunohistochemical localization of orexin-A in human PCa specimens, and the expression of prepro-orexin and OX1 receptor at both protein and mRNA levels in these tissues. Orexin-A administration to the human androgen-dependent prostate carcinoma cells LNCaP up-regulates OX1 receptor expression resulting in a decrease of cell survival. Noteworthy, nanomolar concentrations of the peptide counteract the testosterone-induced nuclear translocation of the androgen receptor in the cells: the orexin-A action is prevented by the addition of the OX1 receptor antagonist SB-408124 to the test system. These findings indicate that orexin-A/OX1 receptor interaction interferes with the activity of the androgen receptor which regulates PCa onset and progression, thus suggesting that orexin-A and its receptor might represent novel therapeutic targets to challenge this aggressive cancer.
Serotonin activates cell survival and apoptotic death responses in cultured epithelial thyroid cells
Biochimie, 2014
Anatomic and physiological interactions between central serotonergic system and thyroid gland are... more Anatomic and physiological interactions between central serotonergic system and thyroid gland are well established. However, the effects of locally available serotonin on the thyroid functions are poorly known. Here, we first demonstrate the expression of serotonin transporter SERT and 5-HT2A receptor subtype in rat thyroid epithelial cell line FRT both at mRNA and protein levels. In order to investigate the molecular mechanisms of serotonin action, FRT cells were exposed to increasing concentrations of the amine. Low concentrations of serotonin (up to 5 μM) enhanced FRT cell growth, and ERK1/2 and SMAD2/3 phosphorylation. Cell exposure to the selective 5-HT2A receptor agonist DOI recapitulated the effects of 5-HT on ERK1/2 phosphorylation. By contrast, administration of M100907, a specific 5-HT2A receptor inhibitor, prevented 5-HT induced ERK1/2 activation. On the other hand, high doses of serotonin (50 μM up to 1 mM) activated a caspase-3 mediated apoptosis of cells. Overall, our findings demonstrate that low levels of serotonin, interacting with 5-HT2A receptor, are able to activate proliferative signals in the thyroid epithelial cells, while high levels of serotonin cause pro-apoptotic responses, thus suggesting an active role of the amine in the thyroid functions and disorders.
Anatomy and Embryology, 1999
The distribution of neurons containing the enzymes NADPH-diaphorase (NADPH-d) and nitric oxide sy... more The distribution of neurons containing the enzymes NADPH-diaphorase (NADPH-d) and nitric oxide synthase (NOS) has been studied in the gastrointestinal tract of lizard (Podarcis s. sicula) and snake (Thamnophis sirtalis). The techniques employed were the NADPHd/nitroblue tetrazolium histochemical method, and the indirect immunofluorescence applied to cryostat sections and to whole-mount preparations. The colocalization of NADPH-d with NOS, with vasoactive intestinal polypeptide (VIP) and with galanin (Gal) was also studied, and a Western blot analysis using an antibody directed against mammalian Gal was performed on lizard stomach extracts. NADPH-d positive nerve cell bodies and fibres were found in the myenteric and submucous plexuses throughout the gastrointestinal tract of both reptiles. These nerve structures were also present in the other intramural nerve plexuses, although in smaller quantities. Both in lizard and snake, the stomach revealed a positive nerve population that was more dense than elsewhere in the gut. The population of the NADPH-d-positive neurons observed in the lizard was larger than that observed in the snake. The distribution of both populations was similar to those that have been described in the gut of several mammalian and non-mammalian vertebrates. Both in lizard and snake, a one-to-one correspondence was noted between NOS-and NADPH-d-containing nerve cell bodies, and the nitrergic neurons containing Gal appeared to be more numerous than those containing VIP. Western blot analysis recognised a single band with a molecular weight (3.4 kDa) very similar to that of por-cine Gal. It is hypothesised that at least some of the nitrergic neurons of the lizard and snake gut are inhibitory motor neurons innervating the circular smooth musculature. In addition, the colocalization of NOS and VIP in neurons enhances their inhibitory action. The role of the neurons containing both NOS and Gal remains unknown.
Autonomic Neuroscience, 2006
Although there is pharmacological evidence to assume that the P2Y 4 receptor is a regulator of ep... more Although there is pharmacological evidence to assume that the P2Y 4 receptor is a regulator of epithelial ion transport, no detailed data about its distribution within the gut are available. Therefore, this study, using whole mounts and cryosections, aimed to reveal the expression pattern of P2Y 4 along the entire guinea-pig gastrointestinal tract. P2Y 4 immunoreactivity was absent from enteric neurons but present in enteric glial cells of the stomach, small and large intestine. In the esophagus, P2Y 4 appeared to be exclusively located within striated muscle cells. P2Y 4 showed also a region dependency regarding its presence in different subpopulations of interstitial cells of Cajal: in myenteric interstitial cells of Cajal in the stomach and ileum; in some intramuscular interstitial cells in the stomach and cecum; in some deep muscular plexus interstitial cells in the ileum; and in some submucosal surface interstitial cells in the colon. These results and the knowledge that P2Y 4 activation causes intracellular Ca 2+ recruitment led us to suggest that P2Y 4 in enteric glia plays a modulatory role in intercellular Ca 2+ waves, while P2Y 4 in interstitial cells of Cajal modulates intracellular Ca 2+ oscillations.
Veterinary research communications, 2017
Infection of kidney cells (MDBK) with Bovine Herpesvirus 1 (BoHV-1) is affected by 2,3,7,8-tetrac... more Infection of kidney cells (MDBK) with Bovine Herpesvirus 1 (BoHV-1) is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which accelerates BoHV-1-induced apoptosis and increases virus replication. Herein, to elucidate the mechanism through TCDD modifies BoHV-1 infection, we analyzed the modulation of a members of Sirtuin proteins family in MDBK cells. We found that mitochondrial SIRT3 was upregulated during infection. This change was accompanied by cytoskeletal rearrangements and cell extensions. All these trends were drastically modified by TCDD. We hypothesize that, taken together, these results might further clarify the processes responsible for the action of TCDD on the BoHV-1 replication, resulting in enhanced virus production.
Biological Psychiatry, 2000
The pacemaker of the biological clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, was... more The pacemaker of the biological clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, was studied in intact male rats to determine its immunoreactivity to glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. Animals were kept under 12-h light-dark cycles in synchrony with day-night periods. Immunohistochemical reactions were carried out at midday and late at night in both winter (January) and summer (July). In winter, GFAP immunoreactivity was found to be low during the day and high at night. The findings were reversed in summer, when GFAP immunoreactivity was high during the day and low at night. Increased GFAP immunoreactivity appeared in the form of an abundance of thick immunopositive fibres rather than of cell bodies. This was interpreted as a hypertrophy of pre-existing astrocytes due to alternating photic stimulation conveyed by retinofugal fibres to the SCN. The observed seasonal reversal in the direction of GFAP oscillations raises the possibility that a circannual timer exists outside the SCN.
Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder
Biological Psychiatry, 2000
Recent postmortem studies in major depressive disorder (MDD) provide evidence for a reduction in ... more Recent postmortem studies in major depressive disorder (MDD) provide evidence for a reduction in the packing density and number of glial cells in different regions of the prefrontal cortex; however, the specific types of glia involved in those morphologic changes are unknown. The territory occupied by the astroglial marker glial fibrillary acidic protein (GFAP) was measured as an areal fraction in cortical layers III, IV, and V in sections from the dorsolateral prefrontal cortex (dlPFC) of MDD and control subjects. In addition, the packing density of GFAP-immunoreactive somata was measured by a direct three-dimensional cell counting method. The mean areal fraction and packing density of GFAP-immunoreactive astrocytes in the dlPFC of MDD subjects were not significantly different from those in control subjects; however, in MDD there was a significant strong positive correlation between age and GFAP immunoreactivity. When the MDD group was divided into younger (30-45 years old) and older (46-86) adults, in the five younger MDD adults, areal fraction and packing density were smaller than the smallest values of the control subjects. In contrast, among older MDD subjects these parameters tended to be greater than in the older control subjects. The present results suggest that the GFAP-immunoreactive astroglia is differentially involved in the pathology of MDD in younger compared with older adults.
Glial fibrillary acidic protein-immunoreactive enteroglial cells in the jejunum of cattle
Acta Histochemica, 2015
Enteroglial cells (EGCs) play critical roles in human health and disease, however, EGC-dependent ... more Enteroglial cells (EGCs) play critical roles in human health and disease, however, EGC-dependent neuropathies also affect commercially important animal species. Due to the lack of data on the distribution and phenotypic characterization of the EGCs throughout the bovine gastrointestinal tract, in this study the topographic localization of EGCs in the jejunum of healthy cattle was investigated by immunofluorescence using the glial specific marker glial fibrillary acidic protein (GFAP) and the panneuronal marker PGP 9.5. This analysis was conducted on both cryosections and whole mount preparations including the myenteric and the submucous plexuses of the bovine jejunum. The results obtained showed the presence of a large subpopulation of GFAP-expressing EGCs in the main plexuses and within the muscle layers, whereas only few GFAP-positive glial processes were found within the deeper layer of the mucosa, and they never reached the mucosal epithelium. Three different EGC subtypes, namely I, III and IV types were recognized in the examined tract of the bovine intestine. Overall, our results provide the basis for future investigations aimed at elucidating the functional role of the GFAP-containing EGCs which is crucial for a better understanding of the physio-pathology of the bovine intestine.
Expression of orexin B and its receptor 2 in rat testis
General and Comparative Endocrinology, 2015
The peptides orexin A (OxA) and orexin B (OxB) deriving from a common precursor molecule, prepro-... more The peptides orexin A (OxA) and orexin B (OxB) deriving from a common precursor molecule, prepro-orexin, by proteolytic cleavage, bind the two G-coupled OX1 and OX2 receptors. While OX1 selectively binds OxA, OX2 shows similar affinity for both orexins. Firstly discovered in the hypothalamus, orexins and their receptors have been found in other brain regions as well as in peripheral tissues of mammals, thus resulting involved in the regulation of a broad variety of physiological functions. While the functional localization of OxA and OX1 in the mammalian genital tract has been already described, the expression of OxB and OX2 and their potential role in the reproductive functions remain to be explored. Here, we investigated the presence of OxB and OX2 in the rat testis by immunohistochemical and biochemical analyses. The results definitely demonstrated the localization of OxB and OX2 in pachytene and second spermatocytes as well as in spermatids at all stages of the cycle of the seminiferous epithelium. The expression of both OX2 mRNA and protein in the rat testis was also established by RT-PCR and Western blotting, respectively. The analysis of the molecular mechanism of action of OxB in the rat testis showed that OxB, in contrast with OxA, is unable to promote steroidogenesis. These results translate into the regulation of diverse biological actions by OxA and OxB in the male gonad.
Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal mouse brain
Synapse, 2015
The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in sever... more The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in several brain regions of chronic morphine exposed adult mice. In this study, the influence of chronic maternal exposure to morphine on the distribution pattern of CB-D28k-expressing neurons in the brain of mouse offspring was investigated. Females of CD-1 mice were daily administered with saline or morphine for 7 days before mating, during the whole gestation period, and until 21 day post-partum. Their offspring were sacrificed on postnatal day 18, and the brains were examined by histology using cresyl violet and by immunohistochemistry using a rabbit polyclonal anti-CB-D28k antibody. Histology revealed no significant differences in the distribution pattern and the number of neurons between the offspring forebrain of the control group of mice and the two groups of mice treated with different doses of morphine. However, immunohistochemical analysis revealed that the number of CB-D28k-immunoreactive neurons remarkably decreased in the cingulate cortex, in the layers II-IV of the parietal cortex and in all regions of the hippocampus, while it increased in the layers V-VI of the parietal cortex and in the subicular region of the offspring brain of morphine treated mice. Overall, our findings demonstrate that maternal exposure to morphine alters the pattern of CB-D28k-expressing neuron pattern in specific regions of murine developing brain, in a layer- and dose-dependent way, thus suggesting that these alterations might represent a mechanism by which morphine modifies the functional aspects of developing brain. This article is protected by copyright. All rights reserved.
Frontiers in Veterinary Science
Orexins A (OXA) and B (OXB) and the receptors 1 (OX1R) and 2 (OX2R) for orexins are hypothalamic ... more Orexins A (OXA) and B (OXB) and the receptors 1 (OX1R) and 2 (OX2R) for orexins are hypothalamic peptides found in several mammalian organs and participated to the control of a wide assortment of physiological and pathological functions. The distribution of OXA and OX1R has been extensively studied in the male gonad of mammals. Here, we examined the expression and localization of OXB and OX2R as well as their possible involvement in the regulation of testicular and epididymal functions, in healthy and cryptorchid dogs, employing some techniques such as immunohistochemistry, Western blotting, and real-time RT-PCR. In vitro tests were also carried out for evaluating the steroidogenic effect of OXB. OXB and OX2R were expressed in spermatocytes, spermatids, and Leydig cells in normal testis. Their localization was restricted to Sertoli and Leydig cells in cryptorchid conditions. OXB was found to be localized in all tracts of both normal and cryptorchid epididymis, whereas OX2R was found...
Animals
Animal-assisted interventions (AAI)s represent the expression of integrated medicine, according t... more Animal-assisted interventions (AAI)s represent the expression of integrated medicine, according to the One Health approach. Actually, animal-assisted therapies and animal-assisted activities are implemented in hospitals, rehabilitation centers, etc. The efficacy of AAIs is based on interspecific interactions and would be impacted by different factors, such as the characters of both the animal and the handler, a suitable selection of animal species, an appropriate animal educational protocol, the relationship between the handler and the animal, and mutual relationship among the animal, the patients, and members of the working team. AAIs produce many advantages for the patients but could expose them to zoonotic-pathogens transmission. Therefore, positive animal welfare, as preventative medicine to avoid incidents or transmission of zoonosis, is a relevant aspect with implications for human and animal health and wellbeing. This review aims to summarize the current published knowledge r...
Neuronal control of the vagina in vertebrates: A review
Acta Histochemica
Animals, 2020
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genu... more Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genus. It is 96.2% homologous to bat CoV RaTG13 and 88% homologous to two bat SARS-like coronaviruses. SARS-CoV-2 is the infectious agent responsible for the coronavirus disease (COVID-19), which was first reported in the Hubei province of Wuhan, China, at the beginning of December 2019. Human transmission from COVID-19 patients or incubation carriers occurs via coughing, sneezing, speaking, discharge from the nose, or fecal contamination. Various strains of the virus have been reported around the world, with different virulence and behavior. In addition, SARS-CoV-2 shares certain epitopes with some taxonomically related viruses, with tropism for the most common synanthropic animals. By elucidating the immunological properties of the circulating SARS-CoV-2, a partial protection due to human–animal interactions could be supposed in some situations. In addition, differential epitopes could be ...
Animal reproduction science, 2018
The steroidogenic enzyme P450 aromatase (ARO) has a key role in the conversion of testosterone (T... more The steroidogenic enzyme P450 aromatase (ARO) has a key role in the conversion of testosterone (T) into estrogens (E), expressed as 17β-estradiol. The presence and localization of this key enzyme have not been described before in the South American camelid alpaca (Vicugna pacos). In our previous studies of the expression and biological effects of orexin A (OxA) and OxB on the alpaca testis demonstrated that OxA, via its specific receptor 1 (OX1R), stimulated T synthesis. In order to extend these findings, we presently explored the presence and localization of ARO in the alpaca male gonad, and the possible correlation between ARO and the orexinergic complex. Western blotting and immunohistochemistry demonstrated the presence of ARO in tissue homogenates and its localization in the tubular and interstitial compartments of the alpaca testis, respectively. The addition of OxA to fresh testicular slices decreased the 17β-estradiol E levels. This effect was annulled by the sequential addi...
BMC veterinary research, Jan 27, 2018
Cryptorchidism is one of the most common birth disorders of the male reproductive system identifi... more Cryptorchidism is one of the most common birth disorders of the male reproductive system identified in dogs and other mammals. This condition is characterised by the absence of one (unilateral) or both (bilateral) gonads from the scrotum. The peptides orexin A (OxA) and B (OxB) were obtained by post-transcriptional proteolytic cleavage of a precursor molecule, called prepro-orexin. These substances bind two types of G-coupled receptors called receptor 1 (OX1R) and 2 (OX2R) for orexins. OX1R is specific to OxA while OX2R binds the two peptides with equal affinity. Orexins modulate a great variety of body functions, such as the reproductive mechanism. The purpose of the present research was to study the presence of OxA and its receptor 1 and their possible involvement in the canine testis under healthy and pathological conditions. This study was performed using adult male normal dogs and male dogs affected by unilateral cryptorchidism. Tissue samples were collected from testes and wer...
Acta histochemica, 2018
The peptides orexin A (OXA) and orexin B (OXB) derived from the proteolytic cleavage of a common ... more The peptides orexin A (OXA) and orexin B (OXB) derived from the proteolytic cleavage of a common precursor molecule, prepro-orexin, were originally described in the rat hypothalamus. Successively, they have been found in many other brain regions as well as in peripheral organs of mammals and other less evolved animals. The widespread localization of orexins accounts for the multiple activities that they exert in the body, including the regulation of energy homeostasis, feeding, metabolism, sleep and arousal, stress, addiction, and cardiovascular and endocrine functions. Both OXA and OXB peptides bind to two G-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R) receptor, though with different binding affinity. Altered expression/activity of orexins and their receptors has been associated with a large number of human diseases. Though at present evidence highlighted a role for orexins and cognate receptors in mammalian reproduction, their central and/or local effects on gonadal func...
Reproduction in Domestic Animals, 2017
The orexins A (OxA) and B (OxB) are two hypothalamic peptides involved in many physiological func... more The orexins A (OxA) and B (OxB) are two hypothalamic peptides involved in many physiological functions of the mammalian body. They act through the binding of two G-coupled receptors named receptor 1 (OX 1 ) and receptor 2 (OX 2 ) for orexins. The first receptor is specific for OxA, while the second binds both the substances with equal affinity. The orexins and the relative receptors have been traced by means of different techniques also at the periphery of the body and particularly in the adrenals, and in gastrointestinal and genital organs. Aim of this work was to investigate the presence of OxB and OX 2 by means of immunohistochemistry and Western blotting analysis in the testis of the South American camelid alpaca, a species primarily breed in Chile and Ecuador and recently diffused in Europe where the quality of its wool is particularly appreciated. OxB immunoreactivity (IR) was found in the tubular compartment of the testis where spermatogonia (resting), zygotene and pachytene spermatocytes, and spermatids clearly showed differently sized and shaped cytoplasmic positive structures. OX 2 -IR was found both in the interstitial and tubular compartments of the testis and particularly in Leydig cells and round and elongated spermatids. Western blotting analysis of testis lysates showed the presence of a protein band whose molecular weight corresponded to that currently assigned to OX 2 . Such findings easily translate the hypothesis that OxB and its receptor 2 play a functional role both in the interstitial and tubular compartments of the alpaca testis.
Journal of neuroscience research, Jan 18, 2017
Over the past century, a huge amount of evidence has emerged pointing to the role of the neurotra... more Over the past century, a huge amount of evidence has emerged pointing to the role of the neurotransmitter serotonin, the neuropeptides orexin A and B, and the small gaseous molecule nitric oxide (NO) (Fig. 1) as crucial regulators of both physiological functions and diseases of the central nervous system (CNS) and peripheral organs as well (Berger et al., 2009; Zhou and Zhu, 2009; Shekhar, 2012). Serotonin, orexins, and NO produced in the brain centrally regulate a great number of neural activities including synaptic plasticity, sleep-wake cycle, energy balance, food intake, hormone secretion, immune responses, cardiovascular functions, and others (Szczepanska-Sadowska et al., 2010; Hu and Zhu, 2014; Shan et al., 2015). Interestingly, these regulatory factors are even involved in the complex neurobiological phenomenon relying on trust, belief, pleasure, and reward activities such as love (Esch and Stefano, 2005). They play major roles in the control of partner preference, sexual desire, erection, copulation, ejaculation, orgasm, and sexual satiety. Serotonin, orexins, NO, and their synthetic and signaling machineries are not limited to the neural tissues and brain, but they are also expressed in peripheral tissues, where their prominent role begins from the time of the morphogenesis in utero and lasts through all of adult life. Peripheral locally produced serotonin, orexins, and NO regulate cardiovascular system physiology, bowel motility, steroidogenesis in the adrenal glands and the genital tract, urethrogenital reflex, vascular smooth muscle contractility, platelet aggregation, immunity, and many other physiological processes (F€ orstermann and Sessa, 2012; Amireault et al., 2013; Li et al., 2014). The regulatory activities of the three neuromodulators depend on the place of their release and the availability of specific receptors; thus, they may exert either stimulatory or inhibitory effects depending on the site of action. An elevated number of disorders affecting either CNS or peripheral organs including psychiatric
Expression and potential role of the peptide orexin-A in prostate cancer
Biochemical and Biophysical Research Communications, 2015
The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved... more The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved in multiple physiological processes in the central nervous system and peripheral organs. Altered expression or signaling dysregulation of orexins and their receptors have been associated with a wide range of human diseases including narcolepsy, obesity, drug addiction, and cancer. Although orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been detected in the human normal and hyperplastic prostate tissues, their expression and function in the prostate cancer (PCa) remains to be addressed. Here, we demonstrate for the first time the immunohistochemical localization of orexin-A in human PCa specimens, and the expression of prepro-orexin and OX1 receptor at both protein and mRNA levels in these tissues. Orexin-A administration to the human androgen-dependent prostate carcinoma cells LNCaP up-regulates OX1 receptor expression resulting in a decrease of cell survival. Noteworthy, nanomolar concentrations of the peptide counteract the testosterone-induced nuclear translocation of the androgen receptor in the cells: the orexin-A action is prevented by the addition of the OX1 receptor antagonist SB-408124 to the test system. These findings indicate that orexin-A/OX1 receptor interaction interferes with the activity of the androgen receptor which regulates PCa onset and progression, thus suggesting that orexin-A and its receptor might represent novel therapeutic targets to challenge this aggressive cancer.
Serotonin activates cell survival and apoptotic death responses in cultured epithelial thyroid cells
Biochimie, 2014
Anatomic and physiological interactions between central serotonergic system and thyroid gland are... more Anatomic and physiological interactions between central serotonergic system and thyroid gland are well established. However, the effects of locally available serotonin on the thyroid functions are poorly known. Here, we first demonstrate the expression of serotonin transporter SERT and 5-HT2A receptor subtype in rat thyroid epithelial cell line FRT both at mRNA and protein levels. In order to investigate the molecular mechanisms of serotonin action, FRT cells were exposed to increasing concentrations of the amine. Low concentrations of serotonin (up to 5 μM) enhanced FRT cell growth, and ERK1/2 and SMAD2/3 phosphorylation. Cell exposure to the selective 5-HT2A receptor agonist DOI recapitulated the effects of 5-HT on ERK1/2 phosphorylation. By contrast, administration of M100907, a specific 5-HT2A receptor inhibitor, prevented 5-HT induced ERK1/2 activation. On the other hand, high doses of serotonin (50 μM up to 1 mM) activated a caspase-3 mediated apoptosis of cells. Overall, our findings demonstrate that low levels of serotonin, interacting with 5-HT2A receptor, are able to activate proliferative signals in the thyroid epithelial cells, while high levels of serotonin cause pro-apoptotic responses, thus suggesting an active role of the amine in the thyroid functions and disorders.
Anatomy and Embryology, 1999
The distribution of neurons containing the enzymes NADPH-diaphorase (NADPH-d) and nitric oxide sy... more The distribution of neurons containing the enzymes NADPH-diaphorase (NADPH-d) and nitric oxide synthase (NOS) has been studied in the gastrointestinal tract of lizard (Podarcis s. sicula) and snake (Thamnophis sirtalis). The techniques employed were the NADPHd/nitroblue tetrazolium histochemical method, and the indirect immunofluorescence applied to cryostat sections and to whole-mount preparations. The colocalization of NADPH-d with NOS, with vasoactive intestinal polypeptide (VIP) and with galanin (Gal) was also studied, and a Western blot analysis using an antibody directed against mammalian Gal was performed on lizard stomach extracts. NADPH-d positive nerve cell bodies and fibres were found in the myenteric and submucous plexuses throughout the gastrointestinal tract of both reptiles. These nerve structures were also present in the other intramural nerve plexuses, although in smaller quantities. Both in lizard and snake, the stomach revealed a positive nerve population that was more dense than elsewhere in the gut. The population of the NADPH-d-positive neurons observed in the lizard was larger than that observed in the snake. The distribution of both populations was similar to those that have been described in the gut of several mammalian and non-mammalian vertebrates. Both in lizard and snake, a one-to-one correspondence was noted between NOS-and NADPH-d-containing nerve cell bodies, and the nitrergic neurons containing Gal appeared to be more numerous than those containing VIP. Western blot analysis recognised a single band with a molecular weight (3.4 kDa) very similar to that of por-cine Gal. It is hypothesised that at least some of the nitrergic neurons of the lizard and snake gut are inhibitory motor neurons innervating the circular smooth musculature. In addition, the colocalization of NOS and VIP in neurons enhances their inhibitory action. The role of the neurons containing both NOS and Gal remains unknown.
Autonomic Neuroscience, 2006
Although there is pharmacological evidence to assume that the P2Y 4 receptor is a regulator of ep... more Although there is pharmacological evidence to assume that the P2Y 4 receptor is a regulator of epithelial ion transport, no detailed data about its distribution within the gut are available. Therefore, this study, using whole mounts and cryosections, aimed to reveal the expression pattern of P2Y 4 along the entire guinea-pig gastrointestinal tract. P2Y 4 immunoreactivity was absent from enteric neurons but present in enteric glial cells of the stomach, small and large intestine. In the esophagus, P2Y 4 appeared to be exclusively located within striated muscle cells. P2Y 4 showed also a region dependency regarding its presence in different subpopulations of interstitial cells of Cajal: in myenteric interstitial cells of Cajal in the stomach and ileum; in some intramuscular interstitial cells in the stomach and cecum; in some deep muscular plexus interstitial cells in the ileum; and in some submucosal surface interstitial cells in the colon. These results and the knowledge that P2Y 4 activation causes intracellular Ca 2+ recruitment led us to suggest that P2Y 4 in enteric glia plays a modulatory role in intercellular Ca 2+ waves, while P2Y 4 in interstitial cells of Cajal modulates intracellular Ca 2+ oscillations.
Veterinary research communications, 2017
Infection of kidney cells (MDBK) with Bovine Herpesvirus 1 (BoHV-1) is affected by 2,3,7,8-tetrac... more Infection of kidney cells (MDBK) with Bovine Herpesvirus 1 (BoHV-1) is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which accelerates BoHV-1-induced apoptosis and increases virus replication. Herein, to elucidate the mechanism through TCDD modifies BoHV-1 infection, we analyzed the modulation of a members of Sirtuin proteins family in MDBK cells. We found that mitochondrial SIRT3 was upregulated during infection. This change was accompanied by cytoskeletal rearrangements and cell extensions. All these trends were drastically modified by TCDD. We hypothesize that, taken together, these results might further clarify the processes responsible for the action of TCDD on the BoHV-1 replication, resulting in enhanced virus production.
Biological Psychiatry, 2000
The pacemaker of the biological clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, was... more The pacemaker of the biological clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, was studied in intact male rats to determine its immunoreactivity to glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. Animals were kept under 12-h light-dark cycles in synchrony with day-night periods. Immunohistochemical reactions were carried out at midday and late at night in both winter (January) and summer (July). In winter, GFAP immunoreactivity was found to be low during the day and high at night. The findings were reversed in summer, when GFAP immunoreactivity was high during the day and low at night. Increased GFAP immunoreactivity appeared in the form of an abundance of thick immunopositive fibres rather than of cell bodies. This was interpreted as a hypertrophy of pre-existing astrocytes due to alternating photic stimulation conveyed by retinofugal fibres to the SCN. The observed seasonal reversal in the direction of GFAP oscillations raises the possibility that a circannual timer exists outside the SCN.
Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder
Biological Psychiatry, 2000
Recent postmortem studies in major depressive disorder (MDD) provide evidence for a reduction in ... more Recent postmortem studies in major depressive disorder (MDD) provide evidence for a reduction in the packing density and number of glial cells in different regions of the prefrontal cortex; however, the specific types of glia involved in those morphologic changes are unknown. The territory occupied by the astroglial marker glial fibrillary acidic protein (GFAP) was measured as an areal fraction in cortical layers III, IV, and V in sections from the dorsolateral prefrontal cortex (dlPFC) of MDD and control subjects. In addition, the packing density of GFAP-immunoreactive somata was measured by a direct three-dimensional cell counting method. The mean areal fraction and packing density of GFAP-immunoreactive astrocytes in the dlPFC of MDD subjects were not significantly different from those in control subjects; however, in MDD there was a significant strong positive correlation between age and GFAP immunoreactivity. When the MDD group was divided into younger (30-45 years old) and older (46-86) adults, in the five younger MDD adults, areal fraction and packing density were smaller than the smallest values of the control subjects. In contrast, among older MDD subjects these parameters tended to be greater than in the older control subjects. The present results suggest that the GFAP-immunoreactive astroglia is differentially involved in the pathology of MDD in younger compared with older adults.
Glial fibrillary acidic protein-immunoreactive enteroglial cells in the jejunum of cattle
Acta Histochemica, 2015
Enteroglial cells (EGCs) play critical roles in human health and disease, however, EGC-dependent ... more Enteroglial cells (EGCs) play critical roles in human health and disease, however, EGC-dependent neuropathies also affect commercially important animal species. Due to the lack of data on the distribution and phenotypic characterization of the EGCs throughout the bovine gastrointestinal tract, in this study the topographic localization of EGCs in the jejunum of healthy cattle was investigated by immunofluorescence using the glial specific marker glial fibrillary acidic protein (GFAP) and the panneuronal marker PGP 9.5. This analysis was conducted on both cryosections and whole mount preparations including the myenteric and the submucous plexuses of the bovine jejunum. The results obtained showed the presence of a large subpopulation of GFAP-expressing EGCs in the main plexuses and within the muscle layers, whereas only few GFAP-positive glial processes were found within the deeper layer of the mucosa, and they never reached the mucosal epithelium. Three different EGC subtypes, namely I, III and IV types were recognized in the examined tract of the bovine intestine. Overall, our results provide the basis for future investigations aimed at elucidating the functional role of the GFAP-containing EGCs which is crucial for a better understanding of the physio-pathology of the bovine intestine.
Expression of orexin B and its receptor 2 in rat testis
General and Comparative Endocrinology, 2015
The peptides orexin A (OxA) and orexin B (OxB) deriving from a common precursor molecule, prepro-... more The peptides orexin A (OxA) and orexin B (OxB) deriving from a common precursor molecule, prepro-orexin, by proteolytic cleavage, bind the two G-coupled OX1 and OX2 receptors. While OX1 selectively binds OxA, OX2 shows similar affinity for both orexins. Firstly discovered in the hypothalamus, orexins and their receptors have been found in other brain regions as well as in peripheral tissues of mammals, thus resulting involved in the regulation of a broad variety of physiological functions. While the functional localization of OxA and OX1 in the mammalian genital tract has been already described, the expression of OxB and OX2 and their potential role in the reproductive functions remain to be explored. Here, we investigated the presence of OxB and OX2 in the rat testis by immunohistochemical and biochemical analyses. The results definitely demonstrated the localization of OxB and OX2 in pachytene and second spermatocytes as well as in spermatids at all stages of the cycle of the seminiferous epithelium. The expression of both OX2 mRNA and protein in the rat testis was also established by RT-PCR and Western blotting, respectively. The analysis of the molecular mechanism of action of OxB in the rat testis showed that OxB, in contrast with OxA, is unable to promote steroidogenesis. These results translate into the regulation of diverse biological actions by OxA and OxB in the male gonad.
Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal mouse brain
Synapse, 2015
The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in sever... more The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in several brain regions of chronic morphine exposed adult mice. In this study, the influence of chronic maternal exposure to morphine on the distribution pattern of CB-D28k-expressing neurons in the brain of mouse offspring was investigated. Females of CD-1 mice were daily administered with saline or morphine for 7 days before mating, during the whole gestation period, and until 21 day post-partum. Their offspring were sacrificed on postnatal day 18, and the brains were examined by histology using cresyl violet and by immunohistochemistry using a rabbit polyclonal anti-CB-D28k antibody. Histology revealed no significant differences in the distribution pattern and the number of neurons between the offspring forebrain of the control group of mice and the two groups of mice treated with different doses of morphine. However, immunohistochemical analysis revealed that the number of CB-D28k-immunoreactive neurons remarkably decreased in the cingulate cortex, in the layers II-IV of the parietal cortex and in all regions of the hippocampus, while it increased in the layers V-VI of the parietal cortex and in the subicular region of the offspring brain of morphine treated mice. Overall, our findings demonstrate that maternal exposure to morphine alters the pattern of CB-D28k-expressing neuron pattern in specific regions of murine developing brain, in a layer- and dose-dependent way, thus suggesting that these alterations might represent a mechanism by which morphine modifies the functional aspects of developing brain. This article is protected by copyright. All rights reserved.