Sandra Cebada-Sánchez

University of Castilla-La Mancha, Toledo, Castille-La Mancha, Spain

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Publications (9)21.43 Total impact

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    ABSTRACT: The postnatal development of the human hippocampal formation establishes the time and place at which we start autobiographical memories. However, data concerning the maturation of the neurochemical phenotypes characteristic of interneurons in the human hippocampus are scarce. We have studied the perinatal and postnatal changes of the dentate gyrus (DG) interneuron populations at three rostrocaudal levels. Immunohistochemically identified neurons and fibers for somatostatin (SOM-12 and SOM-28) and neuropeptide Y (NPY) and the co-localization of SOM-28 and NPY were analyzed. In total, 13 cases were investigated from late pregnancy (1 case), perinatal period (6 cases), first year (1 case), early infancy (3 cases), and late infancy (2 cases). Overall, the pattern of distribution of these peptides in the DG was similar to that of the adult. The distribution of cells was charted, and the cell density (number of positive cells/mm(2)) was calculated. The highest density corresponded to the polymorphic cell layer and was higher at pre- and perinatal periods. At increasing ages, neuron density modifications revealed a decrease from 5 postnatal months onward. In contrast, by late infancy, two immunoreactive bands for SOM-28 and NPY in the molecular layer were much better defined. Double-immunohistochemistry showed that NPY-positive neurons co-localized with SOM-28, whereas some fibers contained only one or other of the neuropeptides. Thus, this peptidergic population, presumably inhibitory, probably has a role in DG maturation and its subsequent functional activity in memory processing.
    Cell and Tissue Research 06/2014; · 3.68 Impact Factor
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    ABSTRACT: Perinatal asphyxia and hypoxia are common causes of morbidity in neonates. Prenatal birth associated with hypoxemia often results in several disorders because of the lack of oxygen in the brain. Survival rates from perinatal hypoxia have improved, but appropriate treatments for recovery are still limited, with great impact on patients, their families, society in general and health systems. The aim of this work is to contribute to a better understanding of the cellular mechanisms underlying the brainstem responses to hypoxia. For this purpose, distributions of two proteins, hypoxia-inducible factor-1 alpha (HIF-1α) and microtubule-associated protein 2 (MAP-2) were analyzed in brainstems of 11 children, four of them showing neuropathological evidence of brain hypoxia. They were included in control or hypoxic groups, and then in several subgroups according to their age. Immunohistochemical labeling for these proteins revealed only cell bodies containing HIF-1α, and both cell bodies and fibers positive for MAP-2 in the children’s brainstems. The distribution of HIF-1α was more restricted than that of MAP-2, and it can be suggested that the expression of HIF-1α increased with age. The distribution pattern of MAP-2 in the medulla oblongata could be more due to age-related changes than to a response to hypoxic damage, whereas in the pons several regions, such as the nucleus ambiguus or the solitary nucleus, showed different immunolabeling patterns in controls and hypoxic cases. The distribution patterns of these two proteins suggest that some brainstem regions, such as the reticular formation or the central gray, could be less affected by conditions of hypoxia.
    Neuroscience 01/2014; 271:77–98. · 3.12 Impact Factor
  • Ricardo Insausti, Sandra Cebada-Sánchez, Pilar Marcos
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    ABSTRACT: The postnatal development of the human hippocampal formation (HF) is subject of increasing interest due to its implication in important pathologies that hamper the normal development of children. In this work, we present a glimpse of the main events that constitute important milestones in the development and shaping of some of the most important psychological capabilities such as autobiographical memory. We analyzed a total of 21 brains ranging from 27 gestational weeks to 14 years. Although we examined some cases in the last trimester of gestation, our description starts at birth, around 40 gestational weeks. Serial sections stained with thionin for Nissl analysis revealed that all fields of the HF were present and identifiable at birth. However, the relative growth of the cortical mantle was much higher relative to the HF. The main structural changes took place during the first postnatal year, in particular in the dentate gyrus and in the entorhinal cortex. At subsequent ages, a growth in size was noted in all components of the HF. This growth was more evident at the body and tail of the hippocampus, as evidenced by measurements of the neuroanatomical series. In addition, we examined in some cases the MRI appearance of the HF at different postnatal ages obtained by postmortem imaging. MRI neuroanatomical series provided anatomically identified landmarks useful for the MRI identification of different components of the HF during postnatal development.
    Advances in anatomy, embryology, and cell biology 01/2010; 206:1-86. · 9.80 Impact Factor
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    ABSTRACT: Hippocampal formation plays a prominent role in episodic memory formation and consolidation. It is likely that episodic memory representations are constructed from cortical information that is mostly funnelled through the entorhinal cortex to the hippocampus. The entorhinal cortex returns processed information to the neocortex. Retrograde tracing studies have shown that neocortical afferents to the entorhinal cortex originate almost exclusively in polymodal association cortical areas. However, the use of retrograde studies does not address the question of the laminar and topographical distribution of cortical projections within the entorhinal cortex. We examined material from 60 Macaca fascicularis monkeys in which cortical deposits of either 3H-amino acids or biotinylated dextran-amine as anterograde tracers were made into different cortical areas (the frontal, cingulate, temporal and parietal cortices). The various cortical inputs to the entorhinal cortex present a heterogeneous topographical distribution. Some projections terminate throughout the entorhinal cortex (afferents from medial area 13 and posterior parahippocampal cortex), while others have more limited termination, with emphasis either rostrally (lateral orbitofrontal cortex, agranular insular cortex, anterior cingulate cortex, perirhinal cortex, unimodal visual association cortex), intermediate (upper bank of the superior temporal sulcus, unimodal auditory association cortex) or caudally (parietal and retrosplenial cortices). Many of these inputs overlap, particularly within the rostrolateral portion of the entorhinal cortex. Some projections were directed mainly to superficial layers (I–III) while others were heavier to deep layers (V–VI) although areas of dense projections typically spanned all layers. A primary report will provide a detailed analysis of the regional and laminar organization of these projections. Here we provide a general overview of these projections in relation to the known neuroanatomy of the entorhinal cortex.
    Journal of Anatomy 06/2007; 211(2):250 - 260. · 2.36 Impact Factor
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    ABSTRACT: The entorhinal cortex is an essential component in the organization of the human hippocampal formation related to cortical activity. It transfers, neocortical information (ultimately distributed to the dentate gyrus and hippocampus) and receives most of the hippocampal output directed to neocortex. At birth, the human entorhinal cortex presents similar layer organization as in adults, although layer II (cell islands) and upper layer III have a protracted maturation. The presence of interneurons expressing calcium-binding proteins (parvalbumin, calbindin-D28K (calbindin) and calretinin) is well documented in the adult human entorhinal cortex. In many of them the calcium binding is co-localized with GABA. Parvalbumin-immunoreactive cells and fibers were virtually absent at birth, their presence increasing gradually in deep layer III, mostly in the lateral and caudal portions of the entorhinal cortex from the 5th month onwards. Calbindin immunoreactive cells and fibers were present at birth, mainly in layers II and upper III; mostly at rostral and lateral portions of the entorhinal cortex, increasing in number and extending to deep layers from the 5th month onwards. Calretinin immunoreactivity was present at birth, homogeneously distributed over layers I, II and upper V, throughout the entorhinal cortex. A substantial increase in the number of calretinin neurons in layer V was observed at the 5th month. The postnatal development of parvalbumin, calbindin and calretinin may have an important role in the functional maturation of the entorhinal cortex through the control of hippocampal, cortical and subcortical information.
    Journal of Chemical Neuroanatomy 01/2004; 26(4):311-6. · 2.48 Impact Factor
  • Ricardo Insausti, Sandra Cebada-Sánchez, Pilar Marcos
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    ABSTRACT: In this section, rather than provide a detailed description of the cellular characteristics of the different fields of the HF, since they have been already extensively reviewed elsewhere (Insausti and Amaral 2004; Amaral and Lavenex 2007), we will focus on the lamination and the global microscopic appearance of the fields, although some superficial notes about the neuronal profiles will be provided as necessary (see Fig. 4.12).
  • Ricardo Insausti, Sandra Cebada-Sánchez, Pilar Marcos
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    ABSTRACT: This section describes the appearance of the HF as it grows postnatally, relating gross anatomical and microscopic features of the HF to its appearance in MRI images. One of the main goals of this part of the study was to compare the MRI appearances of the HF structures with neuroanatomical section series, and to ascertain which specific components of the HF correspond to precise and recognizable landmarks in MRI images. In this way, the landmarks described in the gross anatomical chapter can be applied to the images to facilitate their interpretation in terms of specific components of the HF whenever possible. A secondary objective was to verify whether this comparison would allow the calculation of relative distances of landmarks along the medial temporal lobe, and particularly those related to the HF in the MRI series. Our aim was that this correlation should provide a guide for clinical MRI studies in the postnatal period of development of the human HF. To assess the longitudinal distances at which relevant structures of the HF were located, we chose to use the limen insulae or frontotemporal junction as a fixed starting point, as the temporal poles were not always available. Distances to the limen insulae of anatomical structures that are capable establishing the location and extent of the HF, amygdala and surrounding cortex (PHR) were calculated. Only those pertaining strictly to the HF are presented. For the MRI segmentation we applied our own previously described criteria and segmentation procedure to volumetric evaluation of the temporal pole, EC and PRC in MRI images in adults (Insausti et al. 1998b).
  • Ricardo Insausti, Sandra Cebada-Sánchez, Pilar Marcos
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    ABSTRACT: Macroscopically, both premature cases (not illustrated) and newborns have completely formed brains. Telencephalic structures, such as lobules and commissures and the general topography and disposition of the brain are present. The HF lies at the same position as in the adult: at the ventromedial aspect of the temporal lobe. A gross examination of the brain reveals that the full set of macroscopic landmarks is present in the newborn brain. The utility of this group of gross anatomical landmarks in the segmentation of the HF and the surrounding cortex of the parahippocampal region (PHR, namely the cortical areas around the HF, beginning with the temporopolar cortex, and followed in the caudal direction by the perirhinal and posterior parahippocampal cortices) has been reported previously (Insausti et al. 1998b; Insausti and Amaral 2004).
  • Ricardo Insausti, Sandra Cebada-Sánchez, Pilar Marcos
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    ABSTRACT: Experimental data in nonhuman primates are scarce. However, it has been shown that the fetal hippocampus displays maturation of the dendritic field, as determined by intracellular injection of biocytin, an intracellular marker that completely fills axonal and dendritic arbors so that they can be examined and measured (Khazipov et al. 2001). The results of this unique study indicate that the dendritic arbors of CA1 neurons reach the stratum lacunosum-moleculare by one month before birth (embryonic day E154), and that, by midgestation, synaptic currents can be observed in GABAergic neurons, coincident with the extension of dendritic branches into stratum radiatum, while glutamatergic synapses are associated with the refinement of the dendritic arbor and the appearance of spines during the last third of gestation.