RESUMEN
Introducción: El quiste odontogénico glandular (QOG) tiene una diversidad de características epidemiológicas, clínicas e imagenológicas. El propósito de la presente revisión fue analizarla epidemiología, clínica, imagenología junto con la agresividad, tratamiento, seguimiento y recidiva de QOG en la literatura actual. Materiales y métodos: Se realizó una búsqueda sistemática de casos clínicos de QOG publicados entre 2012-2022 en PubMed, Web of Science y Science Direct que tuvieran información epidemiológica, clínica e imagenológica junto a su confirmación histopatológica a través de descripción e imágenes. Resultados: Se incluyeron 27 artículos con 30QOG. Los QOG se presentaron entre los 7 y 78 años. Su tiempo de evolución promedio fue de un año. Se observaron mayoritariamente en región posterior de mandíbula y sin sintomatología. Mayoritariamente fueron radiolúcidos, uniloculares, con bordes definidos y corticalizados y presentaron expansión ósea. Presentaron características agresivas como gran tamaño, perforación ósea y los dientes involucrados tendieron a tenerespacio periodontal infiltrado, desplazamiento y rizálisis. La mayoría de los QOG se trataron con enucleación y no recidivaron. Conclusiones: Se observaron QOG con características que difieren de la literatura clásica en edad, tiempo de evolución, sintomatología, patrón imagenológico, presentación bilateral y ubicación. La imagenología del QOG tiene un comportamiento por lo general, agresivo. En tanto, su agresividad estuvo asociada con su mayor tamaño, borramiento y/o infiltración cortical, perforación ósea, espacio periodontal infiltrado, rizalisis externa y al compromiso de estructuras anatómicas adyacentes. Teniendo en cuenta estas características, los tratamientos de descompresión y exéresis, junto a seguimientos menores a 5 años podrían recidivar. (AU)
Introduction: Glandular odontogenic cyst (GOC) has a diversity of epidemiological, clinical and imaging characteristics. The purpose of this review was to analyze the epidemiology, clinic, and imaging, along with aggressiveness, treatment, follow-up, and recurrence of GOC in the current literature. Materials and methods: A systematic search for clinical cases of GOC published between 2012-2022 was conducted in PubMed, Web of Science and Science Direct. Epidemiological, clinical and imaging information, along with their histopathological confirmation through description and images had to be present in the articles. Results: 27 articles with 30 GOC were included. GOC was found to be present between 7 and 78 years. Its average evolution time was one year. They were observed mostly in the posterior mandible and were asymptomatic. They were mostly radiolucent, unilocular, with defined and corticated borders and presented bone expansion. They presented aggressive characteristics such as larger size, bone perforation and the teeth involved tended to have infiltrated periodontal space, displacement and root resorption. GOC were mostly treated with enucleation and did not present recurrence. Conclusions: GOC was observed with atypical characteristics, which differ from classical literature in terms of age, time of evolution, symptomatology, imaging pattern, bilateral presentation and location. Imaging of QOG generally has an aggressive behavior. Its aggressiveness was associated with its larger size, cortical effacement and/or infiltration, bone perforation, infiltrated periodontal space, root resorption, and involvement of adjacent anatomical structures. Considering the characteristics mentioned above, decompression and excision treatments, together with follow-up of less than 5 years, could lead to recurrence. (AU)
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Humanos , Quiste Odontogénico Calcificado , Diagnóstico por Imagen , Práctica Profesional , Maxilar , Mandíbula , OdontólogosRESUMEN
Introducción: Los queratinocitos presentes en las células epiteliales del cuerpo humano producen, de manera continuada, pequeñas cantidades de histamina que se mantienen en equilibrio en el epitelio oral. Cuando este equilibro se ve alterado, se produce un aumento de histamina en el tejido oral pudiendo provocar lesiones. Objetivo: En este trabajo de revisión se estudia la relación del exceso de histamina en el Liquen Plano Oral, la Leucoplasia oral y en el Carcinoma Oral de Células Escamosas. Material y método: Búsqueda bibliográfica en la literatura de estudios caso control y retrospectivos acerca del papel de la histamina en el Liquen Plano Oral, la Leucoplasia Oral y el Carcinoma Oral de Células Escamosas. Resultados: Se ha observado un aumento del número de mastocitos y de histamina en los tejidos orales con patología comparado con los tejidos sanos. Conclusión: Este aumento del número de mastocitos y de histamina en los tejidos orales con patología, provocan una desorganización en los precursores de la inflamaciónpudiendo así dañar el epitelio oral. (AU)
Introduction: Keratinocytes present in the epithelial cells of the human body produced, continuously, small amounts of histamine that are kept in balance in the oral epithelium. When this balance is disturbed, there is an increase in histamine in the oral tissue and it can cause injuries. Objective: In this review work we studied the relationship of excess histamine in Oral Lichen Planus, oral Leukoplakia and Oral Squamous Cell Carcinoma. Material and Method: Bibliographic search of the literature of case control and retrospective studies about the role of histamine in Oral Lichen Planus, Oral Leukoplakia and Oral Squamous Cell Carcinoma. Results: An increase in the number of mast cells and histamine has been observed in oral tissues with pathology compared to healthy tissues. Conclusion: This increase in the number of mast cells and histamine in oral tissues with pathology can cause disorganization in the precursors of inflammation and thus can further damage the oral tissue. (AU)
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Humanos , Histamina , Liquen Plano Oral , Leucoplasia , Neoplasias de la Boca , Mastocitos , QueratinocitosRESUMEN
BACKGROUND: Metastases in the oral cavity are rare and account for only 1 to 3% of all malignant lesions in this area. The primary location from which most metastases have been described in the oral cavity in adult patients include lungs, breasts, kidneys and colon. MATERIAL AND METHODS: A systematic search of the literature was carried out following the PRISMA statement in PubMed database. Clinical trials and case series published in the last 10 years [2010-2020] were eligible to be selected. The headings and keywords used in the searches were "cancer" AND "oral metastases", "incidence" AND "oral metastases", "oral metastases" AND "jaw bone", "oral metastases" AND "soft tissue". RESULTS: For the study of the incidence of metastases in the oral cavity, 9 reports of clinical trials and 7 retrospective studies of case series have been included in this article. The primary locations from which more metastases have been described in the oral cavity are lungs (30.6% or 183 cases), breasts (22.2% or 133 cases), liver (15.5% or 93 cases), prostate (9 % or 54 cases), thyroid glands (8.1% or 49 cases), kidneys (7.3% or 44 cases), skin (2.3% or 14 cases), soft tissues (2% or 12 cases), colon (2% or 12 cases) and gastrointestinal (0.6% or 4 cases). These metastases have a predilection for hard tissues. The clinical presentation of these lesions varies from painless granulomatous lesions to lytic areas in the jaws. CONCLUSIONS: Although metastases in the oral cavity is an uncommon pathology, early diagnosis is needed so that in the event that it is the first manifestation, it allows the primary tumor to be diagnosed as soon as possible.
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Neoplasias de la Boca , Adulto , Humanos , Incidencia , Maxilares , Masculino , Neoplasias de la Boca/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: The aim of this study was to determine if the treatment with bisphosphonates other anti-resorptive and antiangiogenic agents influences the success of regenerative and / or implant treatments. MATERIAL AND METHODS: We reviewed the literature from the last 5 years in the PubMed database, using the following words: "Sinus Floor Augmentation"[Mesh] OR "Dental Implants"[Mesh]) OR "Guided Tissue Regeneration"[Mesh]) AND "Osteonecrosis"[Mesh]. The articles were selected following the inclusion and exclusion criteria and were evaluated using the 22 items of the STROBE declaration. The following PICO clinical question was applied: Does the treatment with agents associated with drug osteonecrosis influence the success of regenerative and implant treatments? RESULTS: The initial search resulted in a total of 27 articles. After eliminating those that did not refer to the topic, were duplicated or did not meet the inclusion / exclusion criteria, a full reading of the articles was made evaluating their methodological quality, obtaining six studies with high methodological quality and two with moderate. CONCLUSIONS: The literature regarding this topic is scarce, randomized clinical trials would be necessary to establish protocols relative to implant treatment in patients on antiresorptive treatments. The risk of developing an osteonecrosis associated with the regeneration / implant placement in patients with benign bone diseases is scarce, but it exists and it should not be underestimated. Especially, in the posterior areas of the jaw, if the duration of treatment with BP is greater than 3 years, and if the patient is under therapy with systemic corticosteroids.
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Regeneración Ósea/efectos de los fármacos , Implantes Dentales , Difosfonatos/efectos adversos , Osteonecrosis/inducido químicamente , Animales , Anticuerpos Monoclonales , Bases de Datos Factuales , Implantación Dental Endoósea , Fracaso de la Restauración Dental , Antagonismo de Drogas , Humanos , Elevación del Piso del Seno MaxilarRESUMEN
BACKGROUND: Recently, bone graft materials using permanent teeth have come to light, and clinical and histological outcomes of this material have been confirmed by some studies. The aim of this systematic review was to evaluate the reliability of the autogenous tooth bone graft material applied to alveolar ridge augmentation procedures. MATERIAL AND METHODS: A systematic review of literature was conducted analyzing articles published between 2007 and 2017. The following four outcome variables were defined: a) implant stability b) post-operative complication c) evaluation of implant survival and failure rates, and d) histological analysis. A total of 108 articles were identified; 6 were selected for review. Based on the PICO (problem, intervention, comparison, outcome) model, the chief question of this study was: Can patients with alveolar ridge deficiency be successfully treated with the autogenous teeth used as bone graft? RESULTS: The mean primary stability of the placed implants was 67.3 ISQ and the mean secondary stability was 75.5 ISQ. The dehiscence of the wound was the most frequent complication with a rate of 29.1%. Of the 182 analyzed implants, the survival rate was 97.7% and the failure rate was 2.3%. In the histological analysis, most of studies reported bone formation. CONCLUSIONS: There is insufficient evidence regarding the effects of autogenous teeth used for bone grafting to support any definitive conclusions, although it has been shown clinically safe and good bone forming capacity, and good results are shown about implant stability.
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Aumento de la Cresta Alveolar/métodos , Diente/trasplante , Autoinjertos , HumanosRESUMEN
Los implantes dentales cortos, aunque históricamente se han asociado a un mal pronóstico en las rehabilitaciones orales implantosoportadas, con el paso de los años y los avances en implantología, se han convertido en un tratamiento habitual en la práctica diaria de muchos clínicos, obteniendo tasas de éxito que se han incrementado recientemente hasta prácticamente igualarse a los implantes convencionales para muchos autores. La necesidad de reducir tiempos de trabajo, costes económicos y morbilidad intraoperatoria unida a la creciente demanda derehabilitaciones implanto soportadas en pacientes de un rango de edad cada vez mayor hace necesario añadirlos entre nuestras opciones rehabilitadoras implantológicas. Para ello es necesario conocer sus pros y contras y establecer unos protocolos quirúrgicos y de selección del paciente receptor (AU)
Short dental implants, with the passage of time and advances in implantology, have become astandard treatment in clinical practice. The need to reduce intraoperative time, morbidity and economic costs, linked to the increasing demand for implant rehabilitation in patients with a range of growing old (elder patients) makes it necessary to add the min our rehabilitative implantology options. For this reason, it is important to know its advantages and disadvantages, to set up thesurgical protocols and to select the patients correctly (AU)
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Humanos , Implantación Dental Endoósea/métodos , Anomalías Maxilomandibulares/cirugía , Pérdida de Hueso Alveolar/complicaciones , Aumento de la Cresta Alveolar , Implantes Dentales/clasificaciónRESUMEN
Melatonin is a molecule endogenously produced in a wide variety of immune cells, including mast cells (RBL-2H3). It exhibits immunomodulatory, anti-inflammatory and anti-apoptotic properties. The physiologic mechanisms underlying these activities of melatonin have not been clarified in mast cells. This work is designed to determine the anti-inflammatory effect and mechanism of action of melatonin on activated mast cells. RBL-2H3 were pre-treated with exogenous melatonin (MELx) at physiological (100nM) and pharmacological (1 mM) doses for 30 min, washed and activated with PMACI (phorbol 12-myristate 13-acetate plus calcium ionophore A23187) for 2 h and 12 h. The data shows that pre-treatment of MELx in stimulated mast cells, significantly reduced the levels of endogenous melatonin production (MELn), TNF-α and IL-6. These effects are directly related with the MELx concentration used. MELx also inhibited IKK/NF-κB signal transduction pathway in stimulated mast cells. These results indicate a molecular basis for the ability of melatonin to prevent inflammation and for the treatment of allergic inflammatory diseases through the down-regulation of mast cell activation. J. Cell. Biochem. 117: 1926-1933, 2016. © 2016 Wiley Periodicals, Inc.
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Antiinflamatorios no Esteroideos/farmacología , Mastocitos/inmunología , Melatonina/farmacología , FN-kappa B/inmunología , Transducción de Señal/efectos de los fármacos , Animales , Calcimicina/toxicidad , Línea Celular Tumoral , Interleucina-6/inmunología , Ratas , Transducción de Señal/inmunología , Acetato de Tetradecanoilforbol/toxicidad , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
The lizard Gallotia galloti shows spontaneous and slow axon regrowth through a permissive glial scar after optic nerve axotomy. Although much of the expression pattern of glial, neuronal and extracellular matrix markers have been analyzed by our group, an estimation of the cell loss in the ganglion cell layer (GCL) and the degree of visual function recovery remained unresolved. Thus, we performed a series of tests indicative of effective visual function (pupillary light reflex, accommodation, visually elicited behavior) in 18 lizards at 3, 6, 9 and 12 months post-axotomy which were then processed for immunohistochemistry for the neuronal markers SMI-31 (neurofilaments), Tuj1 (beta-III tubulin) and SV2 (synaptic vesicles) at the last timepoint. Separately, cell loss in the GCL was estimated by comparative quantitation of DAPI(+) nuclei in control and 12 months experimental lizards. Additionally, 15 lizards were processed for electron microscopy to monitor relevant ultrastructural changes in the GCL, optic nerve and optic tract throughout regeneration. Hypertrophy of RGCs was persistent, morphology of the regenerated nerves varied from narrow to neuroma-like features and larger regenerated axons underwent remyelination by 9 months. The estimated cell loss in the GCL was 27% and two-third of the animals recovered the pupillary light reflex which involves the pretectum. Strikingly, visually elicited behavior involving the tectum was only restored in two specimens, presumably due to the higher complexity of this pathway. These preliminary results indicate that limited functional regeneration occurs spontaneously in the severely injured visual system of the lacertid G. galloti.
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Axotomía/métodos , Regeneración Nerviosa/fisiología , Traumatismos del Nervio Óptico/fisiopatología , Nervio Óptico/patología , Recuperación de la Función , Células Ganglionares de la Retina/patología , Visión Ocular/fisiología , Animales , Axones/fisiología , Modelos Animales de Enfermedad , Lagartos , Nervio Óptico/fisiopatología , Nervio Óptico/cirugía , Traumatismos del Nervio Óptico/patologíaRESUMEN
Melatonin is the major secretory product synthesized and secreted by the pineal gland and shows both a wide distribution within phylogenetically distant organisms from bacteria to humans and a great functional versatility. In recent years, a considerable amount of experimental evidence has accumulated showing a relationship between the nervous, endocrine, and immune systems. The molecular basis of the communication between these systems is the use of a common chemical language. In this framework, currently melatonin is considered one of the members of the neuroendocrine-immunological network. A number of in vivo and in vitro studies have documented that melatonin plays a fundamental role in neuroimmunomodulation. Based on the information published, it is clear that the majority of the present data in the literature relate to lymphocytes; thus, they have been rather thoroughly investigated, and several reviews have been published related to the mechanisms of action and the effects of melatonin on lymphocytes. However, few studies concerning the effects of melatonin on cells belonging to the innate immunity have been reported. Innate immunity provides the early line of defense against microbes and consists of both cellular and biochemical mechanisms. In this review, we have focused on the role of melatonin in the innate immunity. More specifically, we summarize the effects and action mechanisms of melatonin in the different cells that belong to or participate in the innate immunity, such as monocytes-macrophages, dendritic cells, neutrophils, eosinophils, basophils, mast cells, and natural killer cells.
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Inmunidad Innata , Melatonina/fisiología , Sistema Mononuclear Fagocítico/inmunología , Animales , Granulocitos/inmunología , Humanos , Células Asesinas Naturales/inmunología , Melatonina/biosíntesis , Melatonina/metabolismoRESUMEN
We studied the histogenesis of the lizard visual system (E30 to adulthood) by using a selection of immunohistochemical markers that had proved relevant for other vertebrates. By E30, the Pax6(+) pseudostratified retinal epithelium shows few newborn retinal ganglion cells (RGCs) in the centrodorsal region expressing neuron- and synaptic-specific markers such as betaIII-tubulin (Tuj1), synaptic vesicle protein-2 (SV2), and vesicular glutamate transporter-1 (VGLUT1). Concurrently, pioneer RGC axons run among the Pax2(+) astroglia in the optic nerve and reach the superficial optic tectum. Between E30 and E35, the optic chiasm and optic tract remain acellular, but the latter contains radial processes with subpial endfeet expressing vimentin (Vim). From E35, neuron- and synaptic-specific stainings spread in the retina and optic tectum, whereas retinal Pax6, and Tuj1/SV2 in RGC axons decrease. Müller glia and abundant optic nerve glia express a variety of glia-specific markers until adulthood. Subpopulations of optic nerve glia are also VGLUT1(+) and cluster differentiation-44 (CD44)-positive but cytokeratin-negative, unlike the case in other regeneration-competent species. Specifically, coexpression of CD44/Vim and glutamine synthetase (GS)/VGLUT1 reflects glial specialization, insofar as most CD44(+) glia are GS(-). In the adult optic tract and tectum, radial glia and free astroglia coexist. The latter show different immunocharacterization (Pax2(-)/CD44(-) /Vim(-)) compared with that in the optic nerve. We conclude that upregulation of Tuj1 and SV2 is required for axonal outgrowth and search for appropriate targets, whereas Pax2(+) optic nerve astroglia and Vim(+) radial glia may aid in early axonal guidance. Spontaneous axonal regrowth seems to succeed despite the heterogeneous mammalian-like glial environment in the lizard optic nerve.
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Diferenciación Celular/fisiología , Lagartos , Neuroglía/fisiología , Neuronas/fisiología , Vías Visuales , Animales , Animales Recién Nacidos , Regulación del Desarrollo de la Expresión Génica/fisiología , Receptores de Hialuranos/metabolismo , Lagartos/anatomía & histología , Lagartos/embriología , Lagartos/crecimiento & desarrollo , Proteínas del Tejido Nervioso/metabolismo , Factor de Transcripción PAX2/metabolismo , Sinapsis/metabolismo , Tubulina (Proteína)/metabolismo , Vías Visuales/citología , Vías Visuales/embriología , Vías Visuales/crecimiento & desarrolloRESUMEN
Sam68 (Src associated in mitosis) is a RNA binding protein that links cellular signaling to RNA processing. In previous studies we found that insulin promotes Sam68 relocalization in the cytoplasm allowing Sam68 to associate with p85PI3K, Grb2, GAP and probably the insulin receptor (IR), modulating insulin action positively. In the present work, we wanted to define the role of Sam68 in the first stages of IR signaling. Both BRET and co-immunoprecipitation assays have been used for the study of Sam68 binding to IR, IRS1 and p85-PI3K. BRET saturation experiments indicated, for the first time, that Sam68 associates with IRS1 in basal condition. To map the region of Sam68 implicated in the interaction with IRS1, different Sam68 mutants deleted in the proline-rich domains were used. The deletion of P0, P1 and P2 proline rich domains in N-terminus as well as P4 and P5 in C-terminus of Sam68 increased BRET(50), thus indicating that the affinity of Sam68 for IRS1 is lower when these domains are missing. Moreover, in IR-transfected HEK-293 cells, BRET saturation experiment indicated that insulin increases the affinity between Sam68-Rluc and IRS1-YFP. In conclusion, our data indicate that Sam68 interacts with IRS-1 in basal conditions, and insulin increases the affinity between these two partners.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antígenos CD/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Proteínas de Unión al ARN/metabolismo , Receptor de Insulina/metabolismo , Células HEK293 , Humanos , Insulina/metabolismo , Insulina/fisiología , Unión Proteica/fisiología , Dominios y Motivos de Interacción de Proteínas/fisiología , Especificidad por Sustrato/fisiologíaRESUMEN
Retinal ganglion cell (RGC) axons regrow spontaneously after optic nerve (ON) transection in G. galloti. Because brain-derived neurotrophic factor (BDNF) is considered the major neurotrophin participating in vertebrate visual system development and promotes RGC survival, we investigated its distribution using dual-labeling immunohistochemistry for neuronal and glial markers. We examined the developing and regenerating lizard visual system at 1, 3, 6, 9, and 12 months postlesion to comparatively evaluate BDNF expression patterns. BDNF was detected from midembryonic stages (E35) in both retinal plexiform layers, and in radial glial processes in the tectum. Moreover, RGC axon staining was detected at late prenatal stages (E39), showing a transient punctate staining which progressed in a temporo-spatial pattern that was similar to myelination. Strong expression in RGC axons was maintained in adults. However, transient downregulation of BDNF staining occurred on the experimental side one month after ON transection followed by a gradual recovery with extensive punctate/swelling distribution and persistent upregulation at 12 months. Conversely, quantitative PCR analysis for 1 and 12 months regenerate lizards showed downregulation of the ratio of BDNF mRNA expression at 12 months and nonsignificant changes of NT-3 transcripts. In summary, we demonstrate that BDNF and NT-3 are abundantly expressed during lizard visual system ontogeny and regeneration suggesting their participation in the development, maintenance and plasticity of the system.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Regeneración Nerviosa/fisiología , Neurotrofina 3/metabolismo , Vías Visuales , Animales , Embrión no Mamífero , Femenino , Lateralidad Funcional , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Lagartos/embriología , Lagartos/fisiología , Masculino , Neuroglía/metabolismo , Neuronas/metabolismo , Traumatismos del Nervio Óptico/patología , Lectinas de Plantas/metabolismo , ARN Mensajero/metabolismo , Retina/citología , Colículos Superiores/embriología , Colículos Superiores/metabolismo , Vimentina/metabolismo , Vías Visuales/embriología , Vías Visuales/metabolismo , Vías Visuales/patologíaRESUMEN
BACKGROUND: Sam68, a member of the signal transduction and activation of RNA metabolism (STAR) family of RNA-binding proteins, has been previously implicated as an adaptor molecule in different signaling systems, including leptin receptor (LEPR) signaling. LEPR activation is known to stimulate JAK-STAT, MAPK and PI3K signaling pathways, thus mediating the biological effects of leptin in different cell types, including trophoblastic cells. We have recently found that leptin stimulation also promotes the overexpression and tyrosine phosphorylation of Sam68 in human trophoblastic JEG-3 cells, suggesting a role for Sam68 in leptin signaling and action in these cells. In the present work, we have studied the participation of Sam68 in the main signaling pathways activated by LEPR to increase growth and proliferation in trophoblastic JEG-3 cells. METHODS: We used an antisense strategy to down-regulate Sam68 expression in these cells, and we studied LEPR signaling by immunoprecipitation and poly-U affinity precipitation and by analyzing phosphorylation levels of signaling proteins by immunoblot. The effect of leptin on protein synthesis and proliferation was studied by ³[H]-leucine and ³[H]-thymidine incorporation. RESULTS: Sam68 knockdown impaired leptin activation of JAK-STAT, PI3K and MAPK signaling pathways in JEG-3 cells. We have also found that leptin-stimulated Sam68 tyrosine phosphorylation is dependent on JAK-2 activity, since the pharmacological inhibitor AG490 prevents the phosphorylation of Sam68 in JEG-3 cells. Finally, the trophic and proliferative effect of leptin in trophoblastic cells is dependent on Sam68 expression, since its down-regulation impaired the leptin-stimulated DNA and protein synthesis. CONCLUSIONS: These data demonstrate that Sam68 participates in the main signaling pathways of LEPR to mediate the trophic and proliferative effect of leptin in human trophoblastic cells.
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Proteínas Adaptadoras Transductoras de Señales/fisiología , Proteínas de Unión al ADN/fisiología , Proteínas de Unión al ARN/fisiología , Receptores de Leptina/fisiología , Transducción de Señal , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Elementos sin Sentido (Genética) , Línea Celular , Proliferación Celular , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Janus Quinasa 2/metabolismo , Leptina/metabolismo , Leptina/farmacología , Fosforilación , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Receptores de Leptina/metabolismo , Factor de Transcripción STAT3/metabolismo , Trofoblastos/metabolismoRESUMEN
Spontaneous regrowth of the axons of retinal ganglion cells (RGC) occurs after unilateral optic nerve transection (ONT) in the lizard Gallotia galloti. We have performed an immunohistochemical and ultrastructural study of the conus papillaris (CP) of this lizard during ontogeny and after ONT in order to characterize its cell subpopulations, innervation and putative blood-brain barrier (BBB) and to evaluate changes occurring throughout regeneration. Proliferating PCNA(+) cells were abundant between embryonic stage 33 (E33) and hatching. From E33, we observed Pax2(+)/GS(+) glial cells in the primitive CP, which became increasingly pigmented and vascularised from E35. Conal astrocytes coexpressing Pax2 with vimentin and/or GFAP were identified from E37-E38. GluT-1(+)/LEA(+)/Pax2(-) endothelial cells (ECs) formed a continuous endothelium with tight junctions and luminal and abluminal microfolds. In adults, the peripheral blood vessels showed a thinner calibre, stronger GluT-1 staining and more abundant microfolds than those of the central CP indicating the higher specialization involved during transport within the former. Occasional pericytes, abundant Pax2(+) pigment cells, LEA(+) microglia/macrophages, unmyelinated Tuj1(+) nerve fibres and SV2(+) synaptic vesicles were also observed in the perivascular zone. After ONT, the expression of GluT-1 and p75(NTR) persisted in ECs, suggesting the preservation/early recovery of the BBB. Relevant ultrastructural alterations were observed at 0.5 months postlesion, although, by 3 months, the CP had recovered the ultrastructure of controls indicating tissue recovery. Abnormal newly formed blood vessels had developed in the CP-optic nerve junction. Thus, the CP is a central nervous system structure whose regenerating capacity might be key for the nutritional support of regenerating RGCs in G. galloti.
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Lagartos/fisiología , Regeneración Nerviosa , Nervio Óptico/fisiología , Animales , Barrera Hematoencefálica/metabolismo , Lagartos/embriología , Neuroglía/citología , Neuroglía/metabolismo , Traumatismos del Nervio Óptico/fisiopatologíaRESUMEN
Spontaneous regrowth of retinal ganglion cell (RGC) axons occurs after optic nerve (ON) transection in the lizard Gallotia galloti. To gain more insight into this event we performed an immunohistochemical study on selected neuron and glial markers, which proved useful for analyzing the axonal regrowth process in different regeneration models. In the control lizards, RGCs were beta-III tubulin- (Tuj1) and HuCD-positive. The vesicular glutamate transporter-1 (VGLUT1) preferentially stained RGCs and glial somata rather than synaptic layers. In contrast, SV2 and vesicular GABA/glycine transporter (VGAT) labeling was restricted to both plexiform layers. Strikingly, the strong expression of glutamine synthetase (GS) in both Müller glia processes and macroglial somata revealed a high glutamate metabolism along the visual system. Upregulation of Tuj1 and HuCD in the surviving RGCs was observed at all the timepoints studied (1, 3, 6, 9, and 12 months postlesion). The significant rise of Tuj1 in the optic nerve head and optic tract (OTr) by 1 and 6 months postlesion, respectively, suggests an increase of the beta-III tubulin transport and incorporation into newly formed axons. Persistent Tuj1(+) and SV2(+) puncta and swellings were abnormally observed in putative degenerating/dystrophic fibers. Unexpectedly, neuron-like cells of obscure significance were identified in the control and regenerating ON-OTr. We conclude that: 1) the persistent upregulation of Tuj1 and HuCD favors the long-lasting axonal regrowth process; 2) the latter succeeded despite the ectopia and dystrophy of some regrowing fibers; and 3) maintenance of the glutamate-glutamine cycle contributes to the homeostasis and plasticity of the system.
Asunto(s)
Biomarcadores/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Lagartos , Regeneración Nerviosa/fisiología , Neuronas/metabolismo , Retina/fisiología , Vías Visuales/fisiología , Animales , Lagartos/anatomía & histología , Lagartos/fisiología , Neuroglía/citología , Neuroglía/fisiología , Neuronas/citología , Traumatismos del Nervio Óptico , Retina/citología , Células Ganglionares de la Retina/fisiología , Sinapsis/metabolismo , Sinapsis/ultraestructura , Vesículas Sinápticas/ultraestructura , Vías Visuales/anatomía & histologíaRESUMEN
We have previously described the spontaneous regeneration of retinal ganglion cell axons after optic nerve (ON) transection in the adult Gallotia galloti. As neurotrophin-3 (NT-3) is involved in neuronal differentiation, survival and synaptic plasticity, we performed a comparative immunohistochemical study of NT-3 during the ontogeny and regeneration (after 0.5, 1, 3, 6, 9, and 12 months postlesion) of the lizard visual system to reveal its distribution and changes during these events. For characterization of NT-3(+) cells, we performed double labelings using the neuronal markers HuC-D, Pax6 and parvalbumin (Parv), the microglial marker tomato lectin or Lycopersicon esculentum agglutinin (LEA), and the astroglial markers vimentin (Vim) and glial fibrillary acidic protein (GFAP). Subpopulations of retinal and tectal neurons were NT-3(+) from early embryonic stages to adulthood. Nerve fibers within the retinal nerve fiber layer, both plexiform layers and the retinorecipient layers in the optic tectum (OT) were also stained. In addition, NT-3(+)/GFAP(+) and NT-3(+)/Vim(+) astrocytes were detected in the ON, chiasm and optic tract in postnatal and adult lizards. At 1 month postlesion, abundant NT-3(+)/GFAP(+) astrocytes and NT-3(-)/LEA(+) microglia/macrophages were stained in the lesioned ON, whereas NT-3 became downregulated in the experimental retina and OT. Interestingly, at 9 and 12 months postlesion, the staining in the experimental retina resembled that in control animals, whereas bundles of putative regrown fibers showed a disorganized staining pattern in the OT. Altogether, we demonstrate that NT-3 is widely distributed in the lizard visual system and its changes after ON transection might be permissive for the successful axonal regrowth.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica/fisiología , Lagartos/fisiología , Regeneración Nerviosa/fisiología , Neurotrofina 3/metabolismo , Traumatismos del Nervio Óptico/fisiopatología , Vías Visuales , Animales , Animales Recién Nacidos , Embrión no Mamífero , Proteínas del Tejido Nervioso/metabolismo , Quiasma Óptico/embriología , Quiasma Óptico/crecimiento & desarrollo , Quiasma Óptico/metabolismo , Vías Visuales/embriología , Vías Visuales/crecimiento & desarrollo , Vías Visuales/metabolismoRESUMEN
Sam68, the substrate of Src in mitosis, belongs to the family of RNA binding proteins. Sam68 contains consensus sequences to interact with other proteins via specific domains. Thus, Sam68 has various proline-rich sequences to interact with SH3 domain-containing proteins. Moreover, Sam68 also has a C-terminal domain rich in tyrosine residues that is a substrate for tyrosine kinases. Tyrosine phosphorylation of Sam68 promotes its interaction with SH2 containing proteins. The association of Sam68 with SH3 domain-containing proteins, and its tyrosine phosphorylation may negatively regulate its RNA binding activity. The presence of these consensus sequences to interact with different domains allows this protein to participate in signal transduction pathways triggered by tyrosine kinases. Thus, Sam68 participates in the signaling of T cell receptors, leptin and insulin receptors. In these systems Sam68 is tyrosine phosphorylated and recruited to specific signaling complexes. The participation of Sam68 in signaling suggests that it may function as an adaptor molecule, working as a dock to recruit other signaling molecules. Finally, the connection between this role of Sam68 in protein-protein interaction with RNA binding activity may connect signal transduction of tyrosine kinases with the regulation of RNA metabolism.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/fisiología , Proteínas de Unión al ARN/fisiología , Transducción de Señal/fisiología , Animales , Proteínas de Unión al ADN , Humanos , Conformación Proteica , ARN/metabolismo , Receptor de Insulina/fisiología , Receptores de Antígenos de Linfocitos T/fisiología , Receptores de Superficie Celular/fisiología , Receptores de LeptinaRESUMEN
Reptiles are the only amniotic vertebrates known to be capable of spontaneous regeneration of the central nervous system (CNS). In this study, we analyzed the reactive changes of glial cells in response to a unilateral physical lesion in the cerebral cortex of the lizard Gallotia galloti, at 1, 3, 15, 30, 120, and 240 days postlesion. The glial cell markers glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), S100 protein, and tomato lectin, as well as proliferating cell nuclear antigen (PCNA) were used to evaluate glial changes occurring because of cortical lesions. A transitory and unilateral upregulation of GFAP and GS in reactive radial glial cells were observed from 15 to 120 days postlesion. In addition, reactive lectin-positive macrophage/microglia were observed from 1 to 120 days postlesion, whereas the expression of S100 protein remained unchanged throughout the examined postlesion period. The matricial zones closest to the lesion site, the sulcus lateralis (SL) and the sulcus septomedialis (SSM), showed significantly increased numbers of dividing cells at 30 days postlesion. At 240 days postlesion, the staining pattern for PCNA, GFAP, GS, and tomato lectin in the lesion site became similar to that observed in unlesioned controls. In addition, ultrastructural data of the lesioned cortex at 240 days postlesion indicated a structural repair process. We conclude that restoration of the glial framework and generation of new neurons and glial cells in the ventricular wall play a key role in the successful structural repair of the cerebral cortex of the adult lizard.
Asunto(s)
Corteza Cerebral/crecimiento & desarrollo , Gliosis/metabolismo , Lagartos/crecimiento & desarrollo , Regeneración Nerviosa/fisiología , Neuroglía/metabolismo , Plasticidad Neuronal/fisiología , Animales , Biomarcadores , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/fisiopatología , Diferenciación Celular/fisiología , División Celular/fisiología , Corteza Cerebral/metabolismo , Corteza Cerebral/ultraestructura , Desnervación , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Inmunohistoquímica , Lagartos/anatomía & histología , Lagartos/metabolismo , Microglía/citología , Microglía/metabolismo , Vías Nerviosas/metabolismo , Vías Nerviosas/ultraestructura , Neuroglía/citología , Neuronas/metabolismo , Neuronas/ultraestructura , Antígeno Nuclear de Célula en Proliferación/metabolismo , Tiempo de Reacción/fisiología , Proteínas S100/metabolismo , Células Madre/citología , Células Madre/metabolismo , Regulación hacia Arriba/fisiologíaRESUMEN
Leptin, the ob gene product, is an adipocyte-secreted hormone that centrally regulates weight by decreasing caloric intake and increasing energy expenditure. Expression of leptin is regulated by dietary status, insulin, glucocorticoids and catecholamines. Pancreastatin (PST), a chromogranin A-derived peptide, correlates with catecholamine levels, and may play a role in the physiology of stress, modulating endocrine secretion and metabolism. Thus, PST has been found to exert a lipolytic and anti-insulin effect in white adipocytes. The aim of the present work was to investigate a possible role of PST modulating the expression of key genes involved in lipid storage and metabolism: leptin, PPAR-gamma2, UCP-1 and UCP-2. We incubated isolated rat epididymal adipocytes with 100 nM PST for 16 and 24 h. Leptin, UCP-2 and UCP-1 mRNA levels were assessed by RT-PCR, followed by Southern blot. Leptin secretion was also measured by ELISA. PST inhibited leptin expression and secretion at 16-h incubation, but this effect was no longer observed after 24 h. On the other hand, PST stimulated the expression of UCP-2 after 16 h. However, the effect was still significant after 24 h. The inhibitory effect of PST on leptin expression and secretion and the stimulation of UCP-2 expression were prevented by blocking PKC. UCP-1 and PPR-gamma2 expression did not change after PST stimulation. Leptin differentially regulates the expression of key genes in the rat adipocyte, upregulating the expression of UCP-2 and inhibiting the expression and secretion of leptin by a mechanism that involves PKC activity. These effects may contribute to the metabolic action of catecholamines in physiological and pathophysiological conditions with increased sympathetic activity.
Asunto(s)
Adipocitos/metabolismo , Leptina/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Hormonas Pancreáticas/metabolismo , Animales , Proteínas Portadoras/metabolismo , Cromogranina A , Canales Iónicos , Leptina/genética , Proteínas de la Membrana/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Ratas , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Proteína Desacopladora 1 , Proteína Desacopladora 2RESUMEN
The role of Sam68, an RNA binding protein and putative substrate of the insulin receptor (IR) in insulin signaling was studied using CHO wild type (WT) cells, CHO cells overexpressing IR, and rat white adipocytes as a physiological system. In CHO-IR cells and adipocytes, Sam68 was tyrosine phosphorylated in response to insulin, and then associated with p85 phosphatidylinositol-3 kinase along with IRS-1. Sam68 was localized mainly in the nucleus of CHO-WT, and both in the nucleus and cytoplasm of CHO-IR cells, but only in the cytoplasm of rat white adipocytes. Insulin stimulation for 16 h enhanced the expression of Sam68 in rat adipocytes and CHO-IR cells. Moreover, CHO-IR cells expressed more Sam68 than CHO-WT, suggesting that overexpression of the IR is enough to induce the expression of Sam68. In summary, these results demonstrate that Sam68 works as a cytoplasmic docking protein which is recruited by IR signaling and whose expression is induced by insulin stimulation, suggesting a putative role for Sam68 in insulin signal transduction.