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R Mendez-Otero

Publications and source records attributed to R Mendez-Otero.

At least 19 recordsLinked to original sources
PubMed2005

Regulation and function of neurogenesis in the adult vertebrate brain.

Most adult tissues retain a reservoir of self-renewing, multipotent stem cells that can generate differentiated tissue components. Until recently, the brain was thought to be an exception to this rule and for many years the pervasive dogma of neurobiology relegated neurogenesis to the embryonic and earlier postnatal stages of development. The discovery of constant neuronal replacement in the adult brain has changed the way we think about neurological diseases and about the exploration of new strategies for brain repair. In this review we will explore the potential of adult neural stem cells and we will present some of our own work on this subject. We will also discuss the possibility that adult neurogenesis and neuronal replacement may also play a role in therapies aimed at restoring impaired brain function. A better understanding of the various aspects of spontaneous neuronal replacement may also be used to increase the success of procedures with cell therapies.

Animals↗
PubMed2004

Expression of neuronal nitric oxide synthase in the developing superficial layers of the rat superior colliculus.

We investigated the level of expression of neuronal nitric oxide synthase (nNOS) in the retinorecipient layers of the rat superior colliculus during early postnatal development. Male and female Lister rats ranging in age between the day of birth (P0) and the fourth postnatal week were used in the present study. Two biochemical methods were used, i.e., in vitro measurement of NOS specific activity by the conversion of [3H]-arginine to [3H]-citrulline, and analysis of Western blotting immunoreactive bands from superior colliculus homogenates. As revealed by Western blotting, very weak immunoreactive bands were observed as early as P0-2, and their intensity increased progressively at least until P21. The analysis of specific activity of NOS showed similar results. There was a progressive increase in enzymatic activity until near the end of the second postnatal week, and a nonsignificant tendency to an increase until the end of the third week was also observed. Thus, these results indicated an increase in the amount of nNOS during the first weeks after birth. Our results confirm and extend previous reports using histochemistry for NADPH-diaphorase and immunocytochemistry for nNOS, which showed a progressive increase in the number of stained cells in the superficial layers during the first two postnatal weeks, reaching an adult pattern at the end of the third week. Furthermore, our results suggested that nNOS is present in an active form in the rat superior colliculus during the period of refinement of the retinocollicular pathway.

Animals↗
PubMed2004

Postnatal expression of the plasticity-related nerve growth factor-induced gene A (NGFI-A) protein in the superficial layers of the rat superior colliculus: relation to N-methyl-D-aspartate receptor function.

Immediate early gene expression in the CNS is induced by sensory stimulation and seems to be involved in long-term synaptic plasticity. We have used an immunohistochemical method to detect the nerve growth factor-induced gene A (NGFI-A) protein expression in the superficial layers of the rat superior colliculus during postnatal development. Our goal was to correlate the expression of this candidate plasticity protein with developmental events, especially the activity-dependent refinement of the retinocollicular and corticocollicular pathways. We have also investigated the N-methyl-D-aspartate (NMDA)-receptor dependence of the NGFI-A expression. Animals of various postnatal ages were used. Postnatal day (P) 12 and older animals were submitted to a protocol of dark adaptation followed by light stimulation. NGFI-A expression was never observed during the first 2 postnatal weeks. The first stained cells were observed at P15, 2 days after eye opening (P13). The highest number of stained cells was observed at the end of the third postnatal week (P22). Adult-like level of expression was reached at P30, since at this age, the number of stained cells was comparable to that found in adult rats (P90). Both P22 animals submitted to an acute treatment with MK-801 (i.p. injection) and adult animals submitted to chronic intracranial infusion of a MK-801 presented a clear decrease in the NGFI-A expression in response to light stimulation. These results suggest that the NGFI-A expression is dependent on the NMDA receptor activation, and the observed pattern of expression is in close agreement with previous descriptions of the changes in the NMDA receptor-mediated visual activity in the developing rat superior colliculus (SC). Our results suggest that the plasticity-related NGFI-A protein might play a role in the developmental plasticity of the superficial layers of the rat SC after eye opening.

Afferent Pathways↗
PubMed2003

Functional role of a specific ganglioside in neuronal migration and neurite outgrowth.

Cell migration occurs extensively during mammalian brain development and persists in a few regions in the adult brain. Defective migratory behavior of neurons is thought to be the underlying cause of several congenital disorders. Knowledge of the dynamics and molecular mechanisms of neuronal movement could expand our understanding of the normal development of the nervous system as well as help decipher the pathogenesis of neurological developmental disorders. In our studies we have identified and characterized a specific ganglioside (9-O-acetyl GD3) localized to the membrane of neurons and glial cells that is expressed in regions of cell migration and neurite outgrowth in the developing and adult rat nervous system. In the present article we review our findings that demonstrate the functional role of this molecule in neuronal motility.

Animals↗
PubMed2003

Distribution of NADPH-diaphorase in the superior colliculus of Cebus monkeys, and co-localization with calcium-binding proteins.

We examined the distribution of the enzyme dihydronicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the superior colliculus (SC) of the New World monkey Cebus apella, and the co-localization of this enzyme with the calcium-binding proteins (CaBPs) calbindin-D28K, parvalbumin and calretinin. Despite the intensely labeled neuropil, rare NADPH-d-positive cells were observed in the stratum griseum superficiale (SGS). Most of the labeled cells in the SC were found in the intermediate layers, with a great number also in the deeper layers. This pattern is very similar to that described in the opossum (Didelphis marsupialis) and in the cat, and different from the pattern found in the rat, which shows labeled cells mainly in the SGS. Cells doubly stained for NADPH-d and CaBPs were observed throughout the SC, although in a small number. Of the NADPH-d-positive cells, 20.3% were doubly labeled for NADPH-d and parvalbumin, 10.2% revealed co-localization with calretinin, and 5.6% with calbindin. The low number of double-stained cells for NADPH-d and the CaBPs indicates that these molecules must participate in different functional circuits within the SC.

Animals↗
PubMed2001

Nitric oxide synthase-positive neurons in the rat superior colliculus: colocalization of NOS with NMDAR1 glutamate receptor, GABA, and parvalbumin.

We analyzed the potential input and output components of nitric oxide synthase (NOS)-containing neurons in the rat superior colliculus (SC). To identify whether NOS-positive neurons receive glutamatergic input we investigated the colocalization of NOS with NMDA receptor subunit R1 (NMDAR1). In addition, to examine whether putative nitric oxide synthesizing neurons represent a neurochemically specific or distinct subpopulation of cells in the SC we studied the colocalization of NOS with the neurotransmitter GABA, the calcium-binding proteins parvalbumin, calbindin and calretinin and with neuropeptides such as somatostatin, substance P and neuropeptide Y. We found that 90% of NOS-positive neurons in the superficial layers of the rat SC express NMDAR1. Nearly 20% of the population of nitridergic neurons also expresses GABA and 15% of them express parvalbumin. NOS-positive neurons in the superior colliculus did not contain calretinin, calbindin or either of the neuropeptides tested. The results of this study show that the capacity for synthesizing NO in the SC is largely restricted to neurons that receive glutamatergic inputs and that some of these neurons express GABA or parvalbumin.

Animals↗
PubMed2001

Expression and function of ganglioside 9-O-acetyl GD3 in postmitotic granule cell development.

We have shown previously that the Jones monoclonal antibody (Jones mAb) recognizes 9-O-acetyl GD3 expressed during periods of neuronal migration and neurite outgrowth in the developing rat nervous system. In the present study we investigated the expression of this ganglioside in the developing cerebellum and correlated this expression with granule cell migration. Electron microscopic immunocytochemistry revealed that around the peak of cerebellar neuronal migration (7-day-old rat), 9-O-acetyl GD3 was localized at the contact sites between migrating granule cells and radial glia in the external granular layer and prospective molecular layer. In addition, using microexplant and slice cultures of the postnatal rat cerebellum, we tested whether the ganglioside detected by our antibody contribute to the regulation of neuronal migration in the cerebellar cortex. We have shown that the Jones mAb blocks the migration of neurons in a dose-dependent manner. These findings suggest strongly that 9-O-acetyl GD3 is involved in granule cell migration in the developing cerebellum.

Animals↗
PubMed2001

Subcellular localization of neuronal nitric oxide synthase in the superficial gray layer of the rat superior colliculus.

The superficial layers of the rat superior colliculus (sSC) receive innervation from retina and include nitric oxide synthase (NOS)-immunoreactive neurons. We used electron microscopic immunocytochemistry to assess the subcellular localization of neuronal NOS (nNOS) in the sSC. nNOS immunoreactivity was detected on the external membrane of mitochondria, endoplasmic reticulum, in pre- and postsynaptic profiles and also diffusely distributed in the cytosol. Postsynaptic labeled regions were often associated with presumptive retinal unlabeled terminals. Microtubules also appeared intensely labeled. These results show that NOS immunoreactive neurons may be innervated by retinal terminals and suggest an association of nNOS with cytoskeletal elements.

Animals↗
PubMed2001

Functional role of a glycolipid in directional movements of neurons.

Migration of neurons from their site of origin to their final destination is a critical and universal step in the formation of the complex structure of the nervous system. The migratory process is thought to be governed in part by genetically and epigenetically defined sequences of signals which are interpreted by migrating cells. The molecular mechanisms that underlie neuronal migration have been the subject of intense investigation. As in other developmental processes, many molecules must participate in neuronal migration. Some molecules, such as cell adhesion molecules and motor proteins, may contribute to discrete steps in the migration act; others, like extracellular signaling molecules, may regulate the activation and/or termination of the migration program. In this article we review findings from our group that demonstrate the functional role(s) of a specific glycolipid in neuronal migration and neurite outgrowth in the developing and adult nervous system.

Animals↗
PubMed2001

The 9-O-acetyl GD3 gangliosides are expressed by migrating chains of subventricular zone neurons in vitro.

Neurons from the anterior subventricular zone (SVZ) of the cerebral cortex migrate tangentially to become interneurons in the olfactory bulb during development and in adult rodents. This migration was defined as neuronophilic, independent of a radial glial substrate. The cortical SVZ and the rostral migratory stream to the olfactory bulb were shown to be rich in 9-O-acetyl GD3 gangliosides (9-O-acGD3), which have been previously shown to be implicated in gliophilic migration in the rodent cerebral cortex and cerebellum. In the present study, we performed SVZ explant cultures using rats during their first postnatal week to analyze the expression of these gangliosides in chain migration of neuronal precursors. We characterized migrating chains of these neuroblasts through morphological analysis and immunocytochemistry for the neural cell adhesion molecule. By using the Jones monoclonal antibody which binds specifically to 9-O-acGD3 we showed that migrating chains from the SVZ explants express 9-O-acGD3 which is distributed in a punctate manner in individual cells. 9-O-acGD3 is also present in migrating chains that form in the absence of radial glia, typical of the neuronophilic chain migration of the SVZ. Our data indicate that 9-O-acetylated gangliosides may participate in neuronophilic as well as gliophilic migration.

Animals↗
PubMed1999

Expression of nitric oxide synthase in the developing rat hippocampus.

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was used to study the development of neurons synthesizing nitric oxide (NO) in the postnatal rat hippocampus. We show that NADPH-d reactive somata and processes are present from the day of birth until adulthood in the Ammon's horn. The dentate gyrus, however, has a more delayed period of nitric oxide synthase (NOS) expression with the staining appearing only by the end of the first postnatal week. Our results suggest that the time course of NOS expression correlates with the developmental sequence of events described in the hippocampus and that NO could be involved in the development of connections in this structure.

Aging↗
PubMed1999

Loss of NADPH diaphorase-positive neurons in the hippocampal formation of chronic pilocarpine-epileptic rats.

Recent evidence suggests an important role for NO in cholinergic models of epilepsy. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), a marker of NO containing neurons, was shown to intensely colocalize with GABA in double-labeling studies performed in the hippocampal formation (exception made for the pyramidal cell layer) (Valtschanoff et al., J Comp Neurol 1993:331:111-121). In this sense, it further characterizes an extremely important cell category due to the relevant involvement of inhibitory systems in the mechanisms of genesis and propagation of seizures. Here, we assessed the histochemistry for NADPHd in the hippocampal complex of chronic pilocarpine-epileptic animals. NADPHd-positive cells were lost in almost every hippocampal subfield in pilocarpine-treated rats. The central portion of the polymorphic layer of the dentate gyrus (hilus) presented one of the highest losses of NADPHd-positive cells (55-79%) in the hippocampus. A significant loss of NADPHd-positive cells was seen in strata oriens, pyramidale, and radiatum CA1, CA2, and CA3 subfields. NADPHd staining in the subicular pyramidal cell layer was not different from that observed in controls. A significant loss of NADPHd-stained cells was observed in entorhinal cortex layers II and III in the epileptic group. For entorhinal cortex layers V and VI, however, results varied from an almost complete tissue destruction to an overexpression of NADPHd-positive cells, as well as an increase in neuropil staining. In summary, loss of NADPHd staining was not uniform throughout the hippocampal formation. There has been a growing support for the notion that GABAergic neurons in the hippocampal formation are not equally sensitive to insults. Our results suggest that, as a marker for a subpopulation of GABAergic neurons, NADPHd helps in further refining the characterization of the different neuronal populations sensitive to epileptic activity.

Animals↗
PubMed1999

Nitric oxide synthase expression in the opossum superior colliculus: a histochemical, immunohistochemical and biochemical study.

The expression of neuronal nitric oxide synthase (nNOS) in the superior colliculus (SC) of the opossum Didelphis marsupialis was studied by NADPH diaphorase (NADPH-d) histochemistry and nNOS immunohistochemistry. In addition, the activity of nNOS was quantified by measurement of [(3)H]-L-arginine conversion to [(3)H]-L-citrulline in tissue extracts from SC superficial layers in opossums and rats. Our results show that the number of NADPH-d stained cells was small and virtually identical in stratum opticum (SO) and stratum griseum superficiale (SGS) and their staining was very light, particularly in SGS. Neuropil staining was heavier in the stratum zonale (SZ) than in SGS or SO. The intermediate and deep layers contained heavily stained cells and moderate neuropil staining. Surprisingly, nNOS-immunoreactive cells were far more numerous than NADPH-d+ cells in every layer. The production of [(3)H]-L-citrulline from [(3)H]-L-arginine in tissue extracts enriched in superficial layers indicated that nNOS specific activity is as high in the opossum as in the rat. Our results suggest that the location of nNOS-expressing neurons in retino-receptive layers may be related to inter-specific differences in the processing of visual information.

Animals↗
PubMed1999

Rapid loss of dorsal horn lectin binding after massive brachial plexus axotomy in young rats.

Lectins are proteins with binding affinities for specific sugars in complex glycoconjugates, some of which have been implicated in limiting synaptic plasticity or modulating nerve growth and guidance. We studied the expression of the glycoconjugate recognized by the isolectin B4 of Griffonia simplicifolia (Gs-IB4) in spinal dorsal horns after massive axotomy of the brachial plexus in weanling rats. Gs-IB4+ binding sites in Rexed's lamina II were rapidly reduced after massive peripheral axotomy. This rapid loss suggests that multiple nerve lesions minimize the number of intact fibers that converge with lesioned fibers into the same cord segments and thus may prevent the plastic changes accompanying the lesion of single nerves.

Animals↗
PubMed1998

Eye enucleation alters intracellular distribution of NO synthase in the superior colliculus.

We investigated the role of retinotectal projections on the distribution of nitric oxide synthase (NOS) in the retinoceptive layers of the rat superior colliculus (SC) using histochemical methods. Rats enucleated at birth showed no alteration in the temporal pattern of NOS expression. There was, however, a dramatic change in the NADPH-diaphorase staining pattern of NOS-positive cells. NOS was absent from the distal portions of the dendritic trees of the deafferented SC. Nevertheless, staining the dendritic trees of these cells with Lucifer yellow showed that they were not morphologically different from those of the ipsilateral SC of monoenucleated animals. The same results were obtained when enucleation was performed in adult rats. We conclude that NOS intracellular distribution in the SC cells can be regulated by retinotectal projections in both developing and adult animals.

Analysis of Variance↗
PubMed1997

Blockage of 9-O-acetyl gangliosides induces microtubule depolymerization in growth cones and neurites.

Gangliosides have been implicated in numerous cellular functions in the developing nervous system. The expression of 9-O-acetyl gangliosides recognized by the JONES mAb correlates with periods of cell migration and axonal pathfinding. In vitro, addition of JONES induces growth cone collapse of dorsal root ganglion neurons. This suggests a modulatory activity of 9-O-acetyl gangliosides on growth cone motility and/or adhesion. In this study we have investigated the effect of JONES mAb addition on the cytoskeleton of dorsal root ganglion neurons in vitro. We have shown that blockage of 9-O-acetyl gangliosides induces the appearance of lateral spikes along the neurites in addition to the effect on the growth cone. Microfilament and microtubular rearrangements accompany these structural modifications. We present evidence that the main effect of JONES mAb is to induce microtubule depolymerization both in growth cones and neurites. Together with the analysis on the spatial distribution of these gangliosides along the cell surface, our results suggest that 9-O-acetyl gangliosides recognized by JONES mAb might serve a concerted action, modulating growth cone motility and axonal branch formation.

Acetylation↗
PubMed1996

Expression of 9-O-acetylated gangliosides in the rat hippocampus.

We have used a monoclonal antibody (Jones mAb) to study the expression of gangliosides associated to neuronal migration in the hippocampus of normal and chronic adult epileptic rats. As in other brain regions, the pattern of expression of this ganglioside in the developing rat hippocampus correlates with the migration of cells and processes. In the adult animal, the ganglioside is not expressed, although neuronal migration and process outgrowth have been described in the dentate gyrus of adult animals. Similar negative results were found in adult animals with pilocarpine induced epilepsy in which abnormal neuronal migration has also been suggested and synaptic reorganization of the dentate mossy fibers has been demonstrated. The current results do not help to explain the molecular basis over which epilepsy, in both human and animal models, leads to mossy fiber sprouting and granule cell dispersion.

Acetylation↗