RESUMEN
PURPOSE OF INVESTIGATION: The aim of this study was to determine the rate of complications in pregnancy and during delivery, as well as neonatal outcomes, in women who underwent in vitro fertilization (IVF) and who are 40 years of age or older. MATERIALS AND METHODS: This was a prospective study. The study group consisted of 29 women who underwent IVF. The control group consisted of women who had a spontaneous pregnancy. RESULTS: Pregnancy complications occurred in 86.21% of women in the study group, an 46.87% of women in the control group. The proportion of cesarean sections (CS) was 84.62% in the study group, and 21.87% in control group. Birth weight < 1,500 grams and < 2,500 grams was present in 17.16% and 22.86% of newborns in the study group, spectively. In the control group, birth weight < 1,500 grams and < 2,500 grams was present in 5.55% and 8.33% of newborns, respectively. Neonatal intensive care unit admissions included 22.86% newborns from the study group and 8.33% from the control group. CONCLUSION: Pregnancy, delivery, and neonatal complications were more frequent in the study (IVF) group.
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Parto Obstétrico , Fertilización In Vitro/métodos , Complicaciones del Embarazo , Adulto , Factores de Edad , Peso al Nacer , Parto Obstétrico/métodos , Parto Obstétrico/estadística & datos numéricos , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Parto , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Estudios Prospectivos , Serbia/epidemiologíaRESUMEN
OBJECTIVE: First trial of estimating values of scans of fetal heart structures (FHS) in first trimester of pregnancy, as more primary facts of possible chromosomopathies. MATERIALS AND METHODS: The study included 2,643 fetuses that were examined in first trimester of pregnancy on Sono CT convex (C5-2MHz), endovaginal (ev 8-4MHz), and linear transducers (L12-5MHz) during a period of eight years. Fetal heart was evaluated using appropriate software with broad-band transducers and color Doppler, Sono CT, and HD ZOOM technologies. The scan was performed by three experienced physicians. FHS were based on: left and right ventricle morphology; AV valves (atrioventricular) position and existence of primal ostium; relationship of left ventricle outflow tract (LVOT) and right ventricle outflow tract (RVOT) and great vessels on three vessel view (3VV) and estimation of ductal and aortic arch. RESULTS: Several developments, one being the ability to identify fetuses at risk for cardiac defects combining nuchal translucency (NT), ductus venosus (DV) Doppler, and evaluation of tricuspid regurgitation, have prompted reconsideration of the role of the first trimester prognostic factor of fetal evaluation. In low-risk pregnancies group, 36 (1.8%) fetuses were found to have congenital heart disease (CHD), and in high-risk pregnancies the number of fetuses with CHD was 75 (12%). Genetic amniocentesis or chorionic villus sampling (CVS) was performed in all fetuses with CHD. Forty-two (37.8%) fetuses with CHD were found to have chromosomal anomalies. Out of 111 fetuses with CHD 39 (35.1%) had an nuchal translucency (NT) above three mm. Out of 42 fetuses with chromosomal anomalies and CHD, 29 (69%) had an increased NT. CONCLUSION: Using first trimester fetal echosonography constitutes a further step in the earlier recognition of chromosomopathies, even in low risk groups. Still further steps are necessary as all facts of good clinical practice. In order to offer further benefits during pregnancies, improvements in diagnostics are still required.
Asunto(s)
Trastornos de los Cromosomas/diagnóstico por imagen , Corazón Fetal/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Medida de Translucencia Nucal , Adolescente , Adulto , Amniocentesis , Muestra de la Vellosidad Coriónica , Trastornos de los Cromosomas/diagnóstico , Estudios de Cohortes , Ecocardiografía , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Humanos , Persona de Mediana Edad , Embarazo , Primer Trimestre del Embarazo , Embarazo de Alto Riesgo , Estudios Prospectivos , Ultrasonografía Prenatal , Venas Umbilicales/diagnóstico por imagen , Adulto JovenRESUMEN
Schizophrenia is a disease of abnormal brain development. Considerable evidence now indicates that environmental factors have a causative role in schizophrenia. Elevated incidence of the disease has been linked to a wide range of disturbances in the prenatal environment and to social factors and drug intake during adolescence. Here we examine neurodevelopment of the prefrontal cortex in the first trimester of gestation and during adolescence to gain further insight into the neurodevelopmental processes that may be vulnerable in schizophrenia. Early embryonic development of the prefrontal cortex is characterized by cell proliferation, including renewal of progenitor cells, generation of early transient cell populations and neurogenesis of subcortical populations. Animal models show that curtailing early gestational cell proliferation produces schizophrenia-like pathology in the prefrontal cortex and mimics key behavioral and cognitive symptoms of the disease. At the other end of the spectrum, elimination of excitatory synapses is the fundamental process occurring during adolescent maturation in the prefrontal cortex. Adverse social situations that elevate stress increase dopamine stimulation of the mesocortical pathway and may lead to exaggerated synaptic pruning during adolescence. In a non-human primate model, dopamine hyperstimulation has been shown to decrease prefrontal pyramidal cell spine density and to be associated with profound cognitive dysfunction. Development of the prefrontal cortex in its earliest stage in gestation and in its final stage in adolescence represents two critical periods of vulnerability for schizophrenia in which cell proliferation and synaptic elimination, respectively, may be influenced by environmental factors.
Asunto(s)
Desarrollo del Adolescente , Corteza Prefrontal/embriología , Corteza Prefrontal/fisiopatología , Esquizofrenia/fisiopatología , Adolescente , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , EmbarazoRESUMEN
Malignant fibrous histiocytoma (MFH) is the most common soft-tissue sarcoma of late adult life occurring predominantly in the extremities and the retroperitoneum. MFH of the ovary is very rare, with only six cases previously reported. A 67-year-old woman with a right pelvic tumor highly suspicious of ovarian carcinoma was submitted to exploratory laparotomy. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, total omentectomy, pelvic and paraaortic lymphadenectomy with right hemicolectomy along with permanent cutaneous ileostomy were performed. Since a storiform-pleomorphic type of MHF was diagnosed from histopathological and immunohistochemical findings, chemotherapy was proposed as the postoperative treatment. Despite extensive surgery with negative surgical margins, the patient had recurrence of the tumor within four months, and was submitted to secondary surgery. A combination of chemo- and radiotherapy was performed postoperatively, but the patient developed respiratory problems and died one year later from the primary diagnosis.
Asunto(s)
Histiocitoma Fibroso Maligno/secundario , Neoplasias Pulmonares/secundario , Recurrencia Local de Neoplasia/cirugía , Neoplasias Ováricas/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Docetaxel , Resultado Fatal , Femenino , Histiocitoma Fibroso Maligno/terapia , Humanos , Neoplasias Ováricas/terapia , Taxoides/administración & dosificación , GemcitabinaRESUMEN
The polysialic acid (PSA) modification of neural cell adhesion molecule, which reduces neural cell adhesion molecule (NCAM) - mediated cell adhesion, is involved in several developmental processes, such as cell migration, axonal growth, path finding, and synaptic plasticity. It has been suggested that PSA-NCAM expression may inhibit myelination. To clarify the relationship between myelination and the expression of PSA-NCAM we systematically investigated its expression in the human forebrain from embryonic stage to midgestation (19-24 gestation weeks, gw). Immunofluorescence on cryosections showed that PSA-NCAM is expressed at the earliest stage studied (5.5 gw) in the primordial plexiform layer of the telencephalon, which mainly consists of neuronal processes. At midgestation, cortical axonal tracts in the emerging white matter were PSA-NCAM+, but they were not yet myelinated, based on the lack of myelin basic protein (MBP) immunoreaction. To follow the progression of myelination we developed organotypic slice cultures that included the subventricular and intermediate zones of the fetal forebrain. In freshly prepared slices, similar to cryosections, axonal tracts were PSA-NCAM+ but did not express MBP. After 5 days in culture there was a dramatic increase in MBP expression around the axons of the intermediate zone, which suggested the onset of myelination. Simultaneously with MBP up-regulation PSA-NCAM expression in axons was completely lost, as demonstrated both with immunofluorescence and Western blot analysis. These results support the idea that in the human fetal forebrain axonal PSA-NCAM expression is inversely related to primary myelination.
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Vaina de Mielina/fisiología , Molécula L1 de Adhesión de Célula Nerviosa/biosíntesis , Prosencéfalo/embriología , Ácidos Siálicos/biosíntesis , Adulto , Axones/metabolismo , Western Blotting , Células Cultivadas , Regulación hacia Abajo/fisiología , Femenino , Feto/metabolismo , Técnica del Anticuerpo Fluorescente , Edad Gestacional , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Vías Nerviosas/embriología , Técnicas de Cultivo de Órganos , EmbarazoRESUMEN
Patient K.N., age 30, nulliparous deliveries and with one miscarriage, was admitted to the Institute of Gynecology and Obstetrics, Clinical Center of Serbia, in December 2000 with the following diagnosis: Uterine myoma and adnexal mass.
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Gonadotropina Coriónica/sangre , Tumor Trofoblástico Localizado en la Placenta/patología , Tumor Trofoblástico Localizado en la Placenta/cirugía , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Adulto , Biopsia con Aguja , Femenino , Estudios de Seguimiento , Humanos , Histerectomía/métodos , Inmunohistoquímica , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Estadificación de Neoplasias , Embarazo , Medición de Riesgo , Resultado del TratamientoRESUMEN
Understanding the factors that govern human forebrain regionalization along the dorsal-ventral and left-right (L-R) axes is likely to be relevant to a wide variety of neurodevelopmental and neuropsychiatric conditions. Recent work in lower vertebrates has identified several critical signaling molecules involved in embryonic patterning along these axes. Among these are the Wingless-Int (WNT) proteins, involved in the formation of dorsal central nervous system (CNS) structures, as well as in visceral L-R asymmetry. We examined the expression of WNT2b and WNT7b in the human brain, because these genes have highly distinctive expression patterns in the embryonic mouse forebrain. In the human fetal telencephalon, WNT2b expression appears to define the cortical hem, a dorsal signaling center previously characterized in mouse, which is also confirmed by BMP7 expression. In diencephalon, WNT2b expression is restricted to medial dorsal structures, including the developing pineal gland and habenular nucleus, both implicated in CNS L-R asymmetry in lower organisms. At 5 weeks gestation, WNT7b is expressed in cerebral cortical and diencephalic progenitor cells. As the cortical plate develops, WNT7b expression shifts, demarcating deep layer neurons of the neocortex and the hippocampal formation. Spatial and temporal expression patterns show startling similarity between human and mouse, suggesting that the developmental roles of these WNT genes may be highly conserved, despite the far greater size and complexity of the human forebrain.
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Regulación del Desarrollo de la Expresión Génica , Prosencéfalo/embriología , Proteínas Proto-Oncogénicas/genética , Animales , Tipificación del Cuerpo , Cartilla de ADN , Embrión de Mamíferos , Femenino , Humanos , Hibridación in Situ , Ratones , Reacción en Cadena de la Polimerasa , Embarazo , Proteínas Proto-Oncogénicas/metabolismo , Especificidad de la EspecieRESUMEN
Chemokines, small proinflammatory cytokines, are involved in migration of inflammatory cells, but also have a role in normal central nervous system development. One chemokine, growth-related oncogene-alpha (GRO-alpha) and its receptor CXCR2, are involved in proliferation and migration of oligodendrocyte progenitors in rats. Here we studied the regional and cell type-specific expression of GRO-alpha and CXCR2 in the human telencephalon at midgestation, the time that oligodendrocytes are being generated in the human brain. Our results showed that both GRO-alpha and CXCR2 are predominately expressed by oligodendrocyte progenitors and activated microglial cells in the highly proliferative subventricular zone. This cellular and regional localization suggests that GRO-alpha/CXCR2 may play a role in human oligodendrocyte proliferation and subsequent migration. We also studied the expression of GRO-alpha and CXCR2 in brain sections of multiple sclerosis (MS) patients. Consistent with their role in the inflammatory process of MS, both GRO-alpha and CXCR2 were expressed in activated microglia localized on the border of MS lesions. However, neither GRO-alpha nor CXCR2 were present in early oligodendrocyte progenitors, a finding that may partially explain why remyelination is not more efficient in MS.
Asunto(s)
Encéfalo/metabolismo , Quimiocinas CXC , Quimiocinas/biosíntesis , Factores Quimiotácticos/biosíntesis , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Esclerosis Múltiple/metabolismo , Oligodendroglía/citología , Receptores de Interleucina-8B/biosíntesis , Astrocitos/metabolismo , Encéfalo/crecimiento & desarrollo , División Celular , Movimiento Celular , Quimiocina CXCL1 , Femenino , Feto , Técnica del Anticuerpo Fluorescente , Humanos , Microglía/citología , Microglía/metabolismo , Neuronas/metabolismo , Oligodendroglía/metabolismo , Embarazo , Células Madre/citología , Células Madre/metabolismo , Regulación hacia ArribaRESUMEN
It has been suggested that Golli proteins, structurally related to myelin basic proteins (MBPs), have a role in autoimmune processes. We studied the expression of these proteins in multiple sclerosis (MS) and determined that the number of Golli-immunoreactive (ir) cells was significantly higher around lesions of chronic MS than in control white matter. Golli proteins were expressed in the adult oligodendrocyte precursor cells (OPCs), activated microglia/macrophages, and some demyelinated axons around MS lesions. Their expression in adult OPCs indicates remyelination attempts, whereas the expression in the subpopulation of microglia/macrophages suggests roles in the immune processes of MS. In addition, Golli proteins may be markers of axonal transection, which is characteristic for MS.
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Química Encefálica , Encéfalo/patología , Esclerosis Múltiple/metabolismo , Proteínas del Tejido Nervioso/análisis , Factores de Transcripción/análisis , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/inmunología , Enfermedad Crónica , Femenino , Humanos , Inmunohistoquímica , Macrófagos/química , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Microglía/química , Microglía/metabolismo , Microglía/patología , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Proteína Básica de Mielina , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/inmunología , Oligodendroglía/química , Oligodendroglía/metabolismo , Oligodendroglía/patología , Células Madre/química , Células Madre/metabolismo , Células Madre/patología , Factores de Transcripción/biosíntesis , Factores de Transcripción/inmunologíaRESUMEN
The myelin basic protein gene (Mbp) encodes for the major myelin structural proteins and it is included in the Golli-Mbp gene complex. Previously, we observed MBP-like proteins in the human central nervous system (CNS) at developmental stages preceding myelination. In an effort to distinguish between Golli (HOG5 and HOG7) and MBP mRNAs and to determine their spatiotemporal distribution, we performed in situ hybridization using two human Golli specific probes: one corresponding to exon 5a absent from all MBP transcripts, and the other corresponding to exon 5c specific for HOG5. HOG7 transcript was observed first, in 5 gestational week-old embryos, whereas both Golli transcripts were detected at 6-7 weeks gestation in the proliferative zones of the entire CNS. Golli proteins immunoreactivity was observed in microglia and early neurons of the developing telencephalon. During midgestation (17-22 weeks gestation), at the onset of myelination, MBP and Golli mRNAs were observed in the telencephalic subventricular zone and occasionally in the future cerebral cortex. Developmental expression of the human Golli-Mbp indicates that the two Golli proteins have different onset of expression, distribution and possibly function. These results support the hypothesis that at least one of them, HOG7, may be involved in the regulation of early neurogenesis, while both may have additional, still undefined function at the onset of myelination.
Asunto(s)
Encéfalo/embriología , Diferenciación Celular/fisiología , Proteína Básica de Mielina/genética , Proteínas del Tejido Nervioso/genética , Neuroglía/metabolismo , Neuronas/metabolismo , Células Madre/metabolismo , Factores de Transcripción/genética , Encéfalo/citología , Encéfalo/metabolismo , Feto , Regulación del Desarrollo de la Expresión Génica/fisiología , Humanos , Inmunohistoquímica , Hibridación in Situ , Lectinas , Vaina de Mielina/metabolismo , Vaina de Mielina/ultraestructura , Proteínas del Tejido Nervioso/metabolismo , Neuroglía/citología , Neuronas/citología , ARN Mensajero/metabolismo , Células Madre/citología , Factores de Transcripción/metabolismo , Tubulina (Proteína)/metabolismoRESUMEN
This study examined glutamate-activated current responses of mouse and human Cajal-Retzius (C-R) cells. Thin cortical slices were prepared from the brains of mice 4-6 days after birth and from those of midgestational human fetuses. Both human and mouse C-R cells displayed glutamate-induced whole-cell current responses that were voltage-dependent and included an N-methyl-D-aspartate (NMDA) receptor-mediated component that was differentially sensitive to blockade by the NMDA receptor antagonists 2-amino-5-phosphonovaleric acid and ifenprodil. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), a non-NMDA glutamate receptor agonist, induced current responses in human but not in mouse C-R cells. These results, taken together, lead us to conclude that human C-R cells express both NMDA and AMPA types of glutamate receptors very early during development of the cortex. In contrast, mouse C-R cells express only the NMDA type of glutamate receptor. Thus we demonstrate a species-dependent sensitivity of C-R cells to glutamate and postulate that this differential sensitivity may account in part for a species-dependent difference in the persistence of C-R cells during cortical development.
Asunto(s)
Ratones/fisiología , Receptores AMPA/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , 2-Amino-5-fosfonovalerato/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Animales , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Conductividad Eléctrica , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Humanos , Técnicas In Vitro , Neuronas/fisiología , Piperidinas/farmacología , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacologíaRESUMEN
Layer I, which plays an important role in the development of the cerebral cortex, expands in size and diversity in primates. We found that, unlike in rodents, in the macaque monkey, neurons of this layer are generated during the entire 2 month period of corticogenesis, within the middle of the 165-d-long gestation. The large, classical Cajal-Retzius cells, immunoreactive to reelin and calretinin but not to GABA, are generated first [embryonic day 38 (E38)-E50], with the peak of [(3)H]thymidine ([(3)H]TdR) labeling at E43. Ultrastructural analysis revealed that processes of these cells form a stereotyped, rectangular network oriented parallel to the pial surface. Genesis of smaller, GABAergic neurons begins slightly later (E43), reaches a peak of [(3)H]TdR labeling between E54 and E70, and continues until the completion of corticogenesis (E94). These late-generated layer I cells are imported from outside sources such as the olfactory primordium and ganglionic eminence and via a massive subpial granular layer that may also supply some GABAergic interneurons to the subjacent cortical plate. The ratio of large-to-small layer I neurons changes differentially, indicating that each class is produced and/or eliminated at a different rate and suggesting that their roles in primates are diverse.
Asunto(s)
Envejecimiento/fisiología , Corteza Cerebral/citología , Corteza Cerebral/embriología , Neuronas/citología , Timidina/análogos & derivados , Animales , Recuento de Células , Corteza Cerebral/metabolismo , Esquema de Medicación , Macaca mulatta , Morfogénesis , Corteza Motora/citología , Corteza Motora/embriología , Corteza Motora/metabolismo , Neuronas/clasificación , Neuronas/metabolismo , Corteza Prefrontal/citología , Corteza Prefrontal/embriología , Corteza Prefrontal/metabolismo , Corteza Somatosensorial/citología , Corteza Somatosensorial/embriología , Corteza Somatosensorial/metabolismo , Timidina/administración & dosificación , Timidina/farmacocinética , Tritio , Corteza Visual/citología , Corteza Visual/embriología , Corteza Visual/metabolismoRESUMEN
In a previous work, mapping early tyrosine hydroxylase (TH) expressing primordia in human embryos, the tegmental origin of the substantia nigra (SN) and ventral tegmental area (VTA) was located across several neuromeric domains: prosomeres 1-3, midbrain, and isthmus (Puelles and Verney, [1998] J. Comp. Neurol. 394:283-308). The present study examines in detail the architecture of the neural wall along this tegmental continuum in 6-7 week human embryos, to better define the development of the SN and VTA. TH-immunoreactive (TH-IR) structures were mapped relative to longitudinal subdivisions (floor plate, basal plate, alar plate), as well as to radially superposed strata of the neural wall (periventricular, intermediate, and superficial strata). These morphologic entities were delineated at each relevant segmental level by using Nissl-stained sections and immunocytochemical mapping of calbindin, calretinin, and GABA in adjacent sagittal or frontal sections. A numerous and varied neuronal population originates in the floor plate area, and some of its derivatives become related through lateral tangential migration with other neuronal populations born in distinct medial and lateral portions of the basal plate and in a transition zone at the border with the alar plate. Some structural differences characterize each segmental domain within this common schema. The TH-IR neuroblasts arise predominantly within the ventricular zone of the floor plate and, more sparsely, within the adjacent medial part of the basal plate. They first migrate radially from the ventricular zone to the pia and then apparently move laterally and slightly rostralward, crossing the superficial stratum of the basal plate. Several GABA-IR cell populations are present in this region. One of them, which might represent the anlage of the SN pars reticulata, is generated in the lateral part of the basal plate.
Asunto(s)
Tipificación del Cuerpo/fisiología , Neuronas/metabolismo , Proteína G de Unión al Calcio S100/metabolismo , Sustancia Negra/embriología , Tirosina 3-Monooxigenasa/metabolismo , Área Tegmental Ventral/embriología , Ácido gamma-Aminobutírico/metabolismo , Factores de Edad , Calbindina 2 , Calbindinas , Diencéfalo/citología , Diencéfalo/embriología , Diencéfalo/metabolismo , Feto , Humanos , Neuronas/citología , Sustancia Negra/citología , Sustancia Negra/metabolismo , Área Tegmental Ventral/citología , Área Tegmental Ventral/metabolismoRESUMEN
A subset of tyrosine-hydroxylase (TH) neurons of the substantia nigra (A9) containing calbindin D28K (CaBP) appeared to be less vulnerable to cell death induced by Parkinson's disease than the subset containing dopamine (DA) alone. Because grafting procedures of fetal human neurons are increasingly used in the therapy of Parkinson's disease, it is important to study the development of DA neurons coexpressing CaBP. In humans, the genesis of TH immunoreactivity of A9, of the ventral tegmental area (A10), and of the retrorubral area (A8) occurred during a 2-week period from the 4. 5th gestational week (g.w.) in the ventricular zone of the floor plate and the contiguous basal plate of the mesencephalon and diencephalon, i.e., the prosomeres p1-p3. Double-immunolabeled TH-CaBP neurons were detected from 5.5 g.w. on, in the first wave of DA neuron's migration, and were observed in their final residence in the dorsal A9 by 10.5 g.w. Calretinin immunoreactivity was expressed in TH-immunoreactive (IR) neurons from 10.5 g.w. on. Ascending TH-CaBP-IR axons were observed toward the telencephalon from 6-7 g.w. , reaching the anlage of the nucleus accumbens and amygdaloid complex at 10.5 g.w., but were not detected in the ganglionic eminence at this latter stage. Dopaminergic patches were detected at 13 g.w. in the anlage of the putamen, but no TH-CaBP-IR fibers were observed in the matrix at this stage. In conclusion, even if CaBP immunoreactivity was detected in TH-IR cell bodies during the embryonic period, the TH-CaBP-IR axonal terminal was observed earlier in some limbic-related areas than in the matrix compartment of the basal ganglia in humans.
Asunto(s)
Dopamina/metabolismo , Vías Nerviosas/embriología , Neuronas/metabolismo , Proteína G de Unión al Calcio S100/metabolismo , Sustancia Negra/embriología , Telencéfalo/embriología , Área Tegmental Ventral/embriología , Axones/metabolismo , Axones/ultraestructura , Trasplante de Tejido Encefálico/métodos , Calbindina 1 , Calbindinas , Muerte Celular/fisiología , Movimiento Celular/fisiología , Trasplante de Tejido Fetal/métodos , Feto , Humanos , Vías Nerviosas/citología , Vías Nerviosas/metabolismo , Neuronas/citología , Neuronas/trasplante , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Sustancia Gris Periacueductal/citología , Sustancia Gris Periacueductal/embriología , Sustancia Gris Periacueductal/metabolismo , Sustancia Negra/citología , Sustancia Negra/metabolismo , Telencéfalo/citología , Telencéfalo/metabolismo , Área Tegmental Ventral/citología , Área Tegmental Ventral/metabolismoRESUMEN
Programmed cell death (PCD) in the form of apoptosis is recognized as one of the central events in the development of the central nervous system. To study the time of onset, extent and distribution of PCD in the human telencephalon, embryos and fetuses from 4.5 to 27 gestational weeks (g.w.) were examined using the TUNEL (TdT-mediated dUTP-biotin nick-end labelling) in situ method. At 4.5 g.w. sparse TUNEL(+) nuclei were observed in the ventricular zone of the neural tube. With the formation of the cortical plate at 7-8 g.w. , TUNEL(+) nuclei were seen in all developmental layers of the cortical anlage, as well as in the subcortical regions such as the ganglionic eminence and the internal capsule. The proliferative zones (the ventricular zone, the subventricular zone and the ganglionic eminence) contained the majority of all apoptotic nuclei observed in each specimen. However, the apoptotic index was highest in the subplate zone and in layer I. Double-labelling experiments suggested that neuronal precursors were the main population of cells undergoing PCD in the first trimester of gestation, whereas glial cells probably start dying around midgestation. The onset of labelling of microglial cells and apoptotic nuclei were synchronous, indicating the involvement of microglia in PCD. In conclusion, two distinct types of PCD were observed during human telencephalic development: embryonic apoptosis, which was synchronous with proliferation and migration of neuronal cells and probably not related to establishment of neuronal circuitry, and fetal apoptosis, which coincided with differentiation and synaptogenesis, and therefore may be related to the development of axonal-target connectivity.
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Apoptosis/fisiología , Telencéfalo/citología , Telencéfalo/embriología , Feto/citología , Humanos , Etiquetado Corte-Fin in Situ , Microglía/fisiología , Microscopía Electrónica , Neuronas/ultraestructura , Células Madre/ultraestructuraRESUMEN
The early expression of reelin, calcium-binding proteins (calretinin, calbindin, and parvalbumin), and neurofilament proteins have been explored in the developing central nervous system of human embryos and fetuses during the first trimester of gestation. Our objective has been to determine further the nature, developmental roles, and contributions of the early neurons and fibers of the original subpial neuropil, i.e., the primordial plexiform layer (PPL). In young embryos (4-5 weeks old), neurofilament protein-labeled fibers run through the subpial neuropil of the caudal portion of the neural tube, reaching the mesencephalon rostrally. At this age, calretinin-immunoreactive and calbindin-immunoreactive neurons are also found among cells already detached from the ventricular zone. The expression of neurofilament protein, calretinin, and calbindin follows an ascending caudorostral gradient, reaching the cerebral vesicles by the 6th-7th week of gestation. In the cerebral cortex, this timing coincides with the initial expression of reelin in the PPL. The reelin immunoreactivity throughout the most superficial cellular population of the cortical PPL supports the early genesis of Cajal-Retzius cells, around the 6th week of gestation. After the splitting of the PPL by the formation of the cortical plate (7-8 weeks of gestation), reelin-immunoreactive cells remain only in the newly established layer I. This study proposes that an initial PPL may be a universal feature of the developing central nervous system.
Asunto(s)
Proteínas de Unión al Calcio/análisis , Embrión de Mamíferos/fisiología , Desarrollo Embrionario y Fetal , Feto/fisiología , Neocórtex/citología , Neocórtex/embriología , Proteínas del Tejido Nervioso/análisis , Calbindina 2 , Calbindinas , Moléculas de Adhesión Celular Neuronal/análisis , Embrión de Mamíferos/anatomía & histología , Proteínas de la Matriz Extracelular/análisis , Femenino , Feto/anatomía & histología , Edad Gestacional , Humanos , Inmunohistoquímica , Fibras Nerviosas/fisiología , Fibras Nerviosas/ultraestructura , Proteínas de Neurofilamentos/análisis , Neuronas/citología , Neuronas/fisiología , Parvalbúminas/análisis , Embarazo , Primer Trimestre del Embarazo , Proteína Reelina , Proteína G de Unión al Calcio S100/análisis , Serina EndopeptidasasRESUMEN
A fundamental question in brain development is how neurons make the precise topographic connections necessary for function. The hypothesis that transient expression of calcium (Ca2+) signaling molecules may have a role in this process was tested by studying human cerebella at midgestation. In addition, four adult brains, two controls and two from patients with ataxia, were studied as well. The temporal and spatial distribution of intracellular Ca2+ channel/receptors, inositol trisphosphate receptor type 1 (IP3R1) and ryanodine receptor (RyR) and three Ca2+ binding proteins were examined with immunocytochemical methods. A positive immune reaction with all markers of Ca2+ signaling was found in the Purkinje cell layer starting from 17 g.w. (gestational weeks), the youngest age studied. The immune reactions were not homogeneous throughout the extent of the Purkinje cell layer, but instead displayed a 'patchy' appearance in all intrauterine stages. In the adult cerebellum the expression of Ca2+ signaling molecules was homogenous. In the two cerebella obtained from patients suffering from ataxia, a several-fold reduction of immunostaining with IP3R1 was found. Our findings suggest that transient and differential mobilization of intracellular Ca2+ in seemingly homogenous neuronal types may play a role in development of highly organized projection maps of the cerebellar cortex. Moreover, lack of IP3R1 in the diseased brains suggests that internal stores of Ca2+ play an important role in normal function of the cerebellum.
Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Ataxia Cerebelosa/metabolismo , Cerebelo/embriología , Adulto , Anciano , Western Blotting , Cadáver , Canales de Calcio/metabolismo , Diferenciación Celular , Cerebelo/metabolismo , Desarrollo Embrionario y Fetal/fisiología , Humanos , Inmunohistoquímica , Receptores de Inositol 1,4,5-Trifosfato , Microscopía Fluorescente , Células de Purkinje/metabolismo , Células de Purkinje/ultraestructura , Receptores Citoplasmáticos y Nucleares/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Sinapsis/fisiologíaRESUMEN
The development of microglia and macrophages was studied in 14 human embryos and fetuses ranging in age from 4.5-13.5 gestational weeks (g.w.), using lectins, Ricinus communis agglutinin-1 [RCA-1], and Lycopersicon esculentum, tomato lectin (TL), which recognize macrophages and microglia, and antibodies for the macrophage antigen CD68. Lectin-positive (+) cells were observed at 4.5 g.w., the youngest age examined. They were detected in the leptomeninges around the neural tube, and only rarely were observed in the CNS parenchyma. At 5.5 g.w., lectin+ cells were present throughout the CNS parenchyma, and a portion of these cells could also be labeled with antibody to CD68. In subsequent weeks, both types of cells, lectin+ and CD68+/lectin+ cells co-existed and progressively developed typical microglial morphology. In addition, in double label experiments, an antibody that labels CD14 antigen present on monocytes, hematogenous precursors of tissue macrophages, did not label either lectin+ or CD68+/lectin+ cells in CNS parenchyma. Additional immunocytochemical studies with appropriate markers excluded the possibility that any of the cells described here were either astrocytes, oligodendrocytes, endothelial cells or neurons. Our finding that one class of cells can be labeled early only with lectins, while another can be labeled with both lectins and CD68 macrophage antibody, may reflect a different origin of microglia in the early embryonic CNS compared to the fetal stages. This subdivision appears to be maintained in the adult brains as well.
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Encéfalo/metabolismo , Lectinas/análisis , Macrófagos/química , Microglía/química , Encéfalo/citología , Encéfalo/embriología , Desarrollo Embrionario y Fetal/fisiología , Edad Gestacional , Histocitoquímica , Humanos , InmunohistoquímicaRESUMEN
Few recent data are available on the development of the precise projection maps of the cerebellar cortex in humans. To address this topic, we studied temporal and spatial distribution of several antigens involved in calcium (Ca)-dependent processes: the intracellular Ca receptors, inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) and ryanodine receptor (RyR); the Ca-binding proteins, calbindin D-28k (CB), parvalbumin (PV), and synaptophysin; and phosphorylated (SMI 31) and nonphosphorylated (SMI 32) forms of neurofilament protein. All antigens were studied in the human cerebellum during intrauterine development. The results of this study show that immunocytochemical markers appeared in the following sequence: CB and both forms ofneurofilament protein were observed at 4-5 gestational weeks (g.w.), PV appeared in the external granular layer and in a few Purkinje cells at 11 g.w., a diffuse immunostaining for IP3R1 and synaptophysin were observed at 13 g.w., whereas RyR was observed at 17-18 g.w. From 24 g.w. on, Purkinje cells expressed all four examined markers of intracellular Ca signaling as well as two forms of neurofilament protein. At the same time, compartmentation of the Purkinje cell layer was detected with three intracellular Ca-signaling molecules (IP3R1, CB, and PV) and with SMI 32. These results indicate that the developmentally regulated expression of antigens studied here may play a role in establishing a highly regular organization of terminal fields in the human cerebellar cortex. Moreover, the initial expression of these antigens is correlated temporally with other developmental processes in the cerebellum, such as cellular maturation, revealed by the immunoreaction to cytoskeletal protein, and synaptogenesis, revealed by immunoreaction to synaptophysin.
Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Cerebelo/embriología , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Neurofilamentos/metabolismo , Vías Aferentes/fisiología , Transporte Biológico/fisiología , Senescencia Celular/fisiología , Cerebelo/metabolismo , Vías Eferentes/fisiología , Desarrollo Embrionario y Fetal/fisiología , Humanos , Fibras Nerviosas/fisiología , Fosforilación , Células de Purkinje/ultraestructura , Sinapsis/fisiologíaRESUMEN
The formation of synapses is among the most important steps in neuronal differentiation and the establishment of neuronal circuits. To establish baseline data about the time of onset, density and the course of synaptic formation in different regions of the human cerebral cortex before birth, synaptogenesis in layer I was examined by electron microscopy in fetuses ranging in age from 6 to 24 gestational weeks. Synapses were first observed in the primordial plexiform layer (marginal zone) in both the lateral and medial cerebral walls between the 6th and 7th gestational week, before the formation of the cortical plate. The density of synapses increased rapidly after the formation of the cortical plate, increasing by 37% between 12 and 14 weeks. Synaptogenesis proceeded at the same rate in the lateral and occipital cortex during this period. Further, with one exception, the insular region, synaptic density was comparable in prospective areas of prefrontal, motor, visual, temporal and cingulate cortex in a group of fetuses at midgestation (20 weeks). The results are consistent with a synchronous course of synaptogenesis of the neocortex.