Biomedical subjects

S E Perez

Publications and source records attributed to S E Perez.

18 recordsLinked to original sources

PubMed2005

Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice.

The functional interactions of the neuropeptide galanin (GAL) occur through its binding to three G protein-coupled receptor subtypes: galanin receptor (GALR) 1, GALR2 and GALR3. Previously, we demonstrated that GALR1 mRNA expression was increased in the CA1 region of the hippocampus and discrete hypothalamic nuclei in galanin transgenic (GAL-tg) mice. This observation suggested a compensatory adjustment in cognate receptors in the face of chronic GAL exposure. To evaluate the molecular alterations to GALR2 and GALR3 in the forebrain of GAL overexpressing mice, we performed complementary quantitative, real-time PCR (qPCR), in situ hybridization, and immunohistochemistry in select forebrain regions of GAL-tg mice to characterize the neuronal distribution and magnitude of GAL mRNA and peptide expression and the consequences of genetically manipulating the neuropeptide GAL on the expression of GALR2 and GALR3 receptors. We found that GAL-tg mice displayed dramatic increases in GAL mRNA and peptide in the frontal cortex, posterior cortex, hippocampus, septal diagonal band complex, amygdala, piriform cortex, and olfactory bulb. Moreover, there was evidence for ectopic neuronal GAL expression in forebrain limbic regions that mediate cognitive and affective behaviors, including the piriform and entorhinal cortex and amygdala. Interestingly, regional qPCR analysis failed to reveal any changes in GALR2 or GALR3 expression in the GAL-tg mice, suggesting that, contrary to GALR1, these receptor genes are not under ligand-mediated regulatory control. The GAL-tg mouse model may provide a useful tool for the investigation of GAL ligand-receptor relationships and their role in normal cognitive and affective functions as well as in the onset of neurological disease.

Animals↗

PubMed2002

Primary infection, latency, and reactivation of bovine herpesvirus type 5 in the bovine nervous system.

Bovine herpesvirus type 5 (BHV-5) infection in calves causes meningoencephalitis, a fatal disease highly prevalent in South America. To study the pathogenesis of BHV-5 infection in cattle, 12 calves (group 1: acute infection) and 11 calves (group 2: latent infection) were intranasally inoculated with an Argentinean BHV-5 isolate at 10(8) and 10(4.7) tissue culture infective doses, respectively; six calves (control group) were mock infected. At 3 months postinoculation, all of the calves in group 2 and three calves in group 3 were given dexamethasone to reactivate the virus. The animals were euthanatized between days 6 and 17 postinoculation (group 1) and between days 6 and 16 postreactivation (group 2). Seventy-five percent and 91% of animals in groups 1 and 2, respectively, excreted BHV-5 in nasal and ocular discharges. Following dexamethasone administration, 45% of calves shed virus in both types of secretions. Spontaneous virus reactivation and shedding was observed in one calf. Neurologic signs consisting of circling, teeth grinding, ptyalism, jaw chomping, tongue protrusion, and apathy were observed in two animals in group 1 and, during the reactivation period, in four animals in group 2. Macroscopic findings consisted of softening of the cerebral tissue, meningeal hemorrhages and swelling, and edema and hemorrhages of prescapular, retropharyngeal and submandibular lymph nodes. Histologic lesions consisted of meningitis, mononuclear perivascular cuffing, neuronophagia, satellitosis, gliosis, hemorrhage, and necrosis and edema. Lesions in anterior cerebral cortex, medulla, and pons were consistently seen in all the animals of group 1. In the acutely infected animals, lesions in the diencephalon appeared at day 10 postinoculation, whereas in the latently infected calves these lesions were observed as early as at day 6 postreactivation. Latently infected animals developed lesions simultaneously in anterior cortex, medulla, pons, and diencephalon, showing a remarkable difference from the acutely infected group. Trigeminal ganglionitis appeared relatively early in animals of both groups (day 7 postinoculation in group 1 and day 8 postreactivation in group 2).

Animals↗

PubMed2001

Galanin: neurobiologic mechanisms and therapeutic potential for Alzheimer's disease.

The neuropeptide galanin (GAL) is widely distributed in the mammalian CNS. Several lines of evidence suggest that GAL may play a critical role in cognitive processes such as memory and attention through an inhibitory modulation of cholinergic basal forebrain activity. Furthermore, GAL fibers hyperinnervate remaining cholinergic basal forebrain neurons in Alzheimer's disease (AD). This suggests that GAL activity impacts cholinergic dysfunction in advanced AD. Pharmacological and in vitro autoradiographic studies indicate the presence of heterogeneous populations of GAL receptor (GALR) sites in the basal forebrain which bind GAL with both high and low affinity. Interestingly, we have recently observed that GALR binding sites increase in the anterior basal forebrain in late-stage AD. Three G protein-coupled GALRs have been identified to date that signal through a diverse array of effector pathways in vitro, including adenylyl cyclase inhibition and phospholipase C activation. The repertoire and distribution of GALR expression in the basal forebrain remains unknown, as does the nature of GAL and GALR plasticity in the AD basal forebrain. Recently, GAL knockout and overexpressing transgenic mice have been generated to facilitate our understanding of GAL activity in basal forebrain function. GAL knockout mice result in fewer cholinergic basal forebrain neurons and memory deficits. On the other hand, mice overexpressing GAL display hyperinnervation of basal forebrain and memory deficits. These data highlight the need to explore further the putative mechanisms by which GAL signaling might be beneficial or deleterious for cholinergic cell survival and activity within basal forebrain. This information will be critical to understanding whether pharmacological manipulation of GALRs would be effective for the amelioration of cognitive deficits in AD.

Alzheimer Disease↗

PubMed2000

Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo.

The neuron-restrictive silencer factor (NRSF; also known as REST for repressor element-1 silencing transcription factor) is a transcriptional repressor of multiple neuronal genes, but little is known about its function in vivo. NRSF is normally down-regulated upon neuronal differentiation. Constitutive expression of NRSF in the developing spinal cord of chicken embryos caused repression of two endogenous target genes, N-tubulin and Ng-CAM, but did not prevent overt neurogenesis. Nevertheless, commissural neurons that differentiated while constitutively expressing NRSF showed a significantly increased frequency of axon guidance errors. These data suggest that down-regulation of NRSF is necessary for the proper development of at least some classes of neurons in vivo.

Animals↗

PubMed2000

Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells.

The genesis of vertebrate peripheral ganglia poses the problem of how multipotent neural crest stem cells (NCSCs) can sequentially generate neurons and then glia in a local environment containing strong instructive neurogenic factors, such as BMP2. Here we show that Notch ligands, which are normally expressed on differentiating neuroblasts, can inhibit neurogenesis in NCSCs in a manner that is completely dominant to BMP2. Contrary to expectation, Notch activation did not maintain these stem cells in an uncommitted state or promote their self-renewal. Rather, even a transient activation of Notch was sufficient to cause a rapid and irreversible loss of neurogenic capacity accompanied by accelerated glial differentiation. These data suggest that Notch ligands expressed by neuroblasts may act positively to instruct a cell-heritable switch to gliogenesis in neighboring stem cells.

Animals↗

PubMed1999

Kinesin-II is required for axonal transport of choline acetyltransferase in Drosophila.

KLP64D and KLP68D are members of the kinesin-II family of proteins in Drosophila. Immunostaining for KLP68D and ribonucleic acid in situ hybridization for KLP64D demonstrated their preferential expression in cholinergic neurons. KLP68D was also found to accumulate in cholinergic neurons in axonal obstructions caused by the loss of kinesin light chain. Mutations in the KLP64D gene cause uncoordinated sluggish movement and death, and reduce transport of choline acetyltransferase from cell bodies to the synapse. The inviability of KLP64D mutations can be rescued by expression of mammalian KIF3A. Together, these data suggest that kinesin-II is required for the axonal transport of a soluble enzyme, choline acetyltransferase, in a specific subset of neurons in Drosophila. Furthermore, the data lead to the conclusion that the cargo transport requirements of different classes of neurons may lead to upregulation of specific pathways of axonal transport.

Amino Acid Sequence↗

PubMed1999

Early specification of sensory neuron fate revealed by expression and function of neurogenins in the chick embryo.

The generation of sensory and autonomic neurons from the neural crest requires the functions of two classes of basic helix-loop-helix (bHLH) transcription factors, the Neurogenins (NGNs) and MASH-1, respectively (Fode, C., Gradwohl, G., Morin, X., Dierich, A., LeMeur, M., Goridis, C. and Guillemot, F. (1998) Neuron 20, 483-494; Guillemot, F., Lo, L.-C., Johnson, J. E., Auerbach, A., Anderson, D. J. and Joyner, A. L. (1993) Cell 75, 463-476; Ma, Q., Chen, Z. F., Barrantes, I. B., de la Pompa, J. L. and Anderson, D. J. (1998 Neuron 20, 469-482). We have cloned two chick NGNs and found that they are expressed in a subset of neural crest cells early in their migration. Ectopic expression of the NGNs in vivo biases migrating neural crest cells to localize in the sensory ganglia, and induces the expression of sensory neuron-appropriate markers in non-sensory crest derivatives. Surprisingly, the NGNs can also induce the expression of multiple pan-neuronal and sensory-specific markers in the dermomyotome, a mesodermal derivative. Taken together, these data suggest that a subset of neural crest cells may already be specified for a sensory neuron fate early in migration, as a consequence of NGN expression.

Amino Acid Sequence↗

PubMed1996

Organisation of the cerebellar nucleus of the dogfish, Scyliorhinus canicula L.: a light microscopic, immunocytochemical, and ultrastructural study.

Elasmobranchs possess a well-developed cerebellum with an associated cerebellar nucleus. To determine whether the organization of this nucleus is comparable with that of the deep cerebellar nuclei of mammals, we studied the dogfish cerebellar nucleus with light microscopic methods (Nissl stain, Golgi method, reduced silver stain, NADPH-diaphorase histochemistry and immunocytochemistry) and with electron microscopy. We found the dogfish cerebellar nucleus to consist of about 1,050 large neurons, the ratio of Purkinje cells to cerebellar nucleus neurons being about 17:1. Immunocytochemistry showed large glutamatergic neurons in the main portions of the nucleus and small glutamate- and/or alpha-aminobutyric acid (GABA)-immunoreactive cells in the subventricular region of the nucleus. Large glutamatergic neurons corresponded to bipolar or triangular cells revealed by Golgi methods. Application of horseradish peroxidase to the cerebellar cortex produced the labelling of beaded fibres of Purkinje cells in the cerebellar nucleus. Unlike in mammals, GABAergic innervation of the cerebellar nucleus was scare: Purkinje cell axon terminals in the cerebellar nucleus did not appear to be GABA-immunoreactive, most GABAergic fibres being found in the subventricular neuropile. Some fibres immunoreactive to serotonin and somatostatin were also observed in the subventricular neuropile of the cerebellar nucleus. Three neuron types were distinguished with electron microscopy (types A to C). Type A cells were abundant and smooth-surfaced, and appeared to correspond to Golgi-impregnated neurons and large glutamate-immunoreactive cells. Type B neurons were scarce and possessed dendrites covered by sessile or stalked spines. Type C neurons were small cells located mainly in the medialmost region of the nucleus and corresponded to subventricular glutamate- and GABA-immunoreactive cells. Six types of synaptic bouton were observed (types I to VI). The most abundant (type I boutons) made symmetrical contacts and appeared to correspond to Purkinje cell axons. Type I boutons were the only type observed on perikarya and initial axon segments of type A cells. Type IV and type V boutons made complex glomerular-like asymmetrical contacts with spines of type B cells. Type VI boutons appeared to correspond to peptidergic and/or monoaminergic axons. The functional significance of these results is discussed.

Animals↗

PubMed1996

NADPH-diaphorase histochemistry reveals oligodendrocytes in the rainbow trout (teleosts).

We studied the distribution of NADPH-diaphorase (NADPHd) in the brain of the rainbow trout. Not only neurons but also tanycytes and oligodendrocytes showed NADPHd positivity. Interestingly, staining of oligodendrocytes was delicate and revealed fine characteristics of these cells, comparable to those revealed by classical 'oligodendrocyte methods' in mammals (such as the rich branching of processes and their association with myelin sheaths). NADPHd histochemistry indicated that trout oligodendrocytes are heterogeneous as regards cell size, shape and number of processes, and that there is a positive correlation between the size of axons and that of the associated oligodendrocytes. NADPHd histochemistry thus appears to be a useful method for the study of oligodendrocyte populations in bony fishes. Furthermore, this is the first report of NADPHd activity in oligodendrocytes of any vertebrate.

Animals↗

PubMed1996

Migration of glial cells into retinal axon target field in Drosophila melanogaster.

During the development of the Drosophila visual system, photoreceptor (retinal) axons (R axons) project retino-topically to their targets in the optic lobes. The establishment of this precise pattern of connections does not depend on interactions between adjacent axon bundles, suggesting that R axons rely on environmental signals for proper pathfinding. Glial cells that are located along the R-axon trajectory are likely candidates to provide guidance cues for R-axon navigation. This study defines the origin of lamina glia (L glia), and demonstrates that L glia migrate into the lamina over a considerable distance. Glia are located in positions at which the R axons make critical growth choices. In the absence of cues from the eye, several classes of glia migrate to their final positions within the optic lobe anlage and begin to differentiate. Our results are consistent with a role for the glia in providing guidance cues to the R axons.

Animals↗

PubMed1996

Molecular and genetic analyses of lama, an evolutionarily conserved gene expressed in the precursors of the Drosophila first optic ganglion.

Drosophila retinal axons trigger both the proliferation of their targets, the lamina neurons, as well as the final differentiation and migration of the lamina glia. To date, the molecular basis of these interactions has remained unclear. We have identified a new gene, lamina ancestor (lama). Both the lamina's neural and glial progenitors express lama, even though these cells have very different developmental origins. Expression of lama is down-regulated once the precursors begin their differentiation programs. Loss of function mutants are viable and fertile, and appear to have normally developed visual systems. lama encodes a novel protein that is 74% identical to its D. virilis homologue.

Amino Acid Sequence↗

PubMed1992

Directionality of menstrual flow: cervical os diameter as a determinant of retrograde menstruation.

OBJECTIVE: To develop a mathematical model to examine the factors that control the directionality of menstrual flow. DESIGN: The model consisted of a rigid cavity, filled with a viscous liquid, with three outflow ports: a set of paired outflow ports (fallopian tube ostia) and an additional single outflow port (cervical os). The Darcy-Weisbach equation was used to calculate flow rates through the ports. RESULTS: At cervical os diameters of less than 0.5 mm, more than 50% of flow was through the fallopian tubes over a wide range of values for cervical length and fallopian tube ostia diameter and length. The diameter of the fallopian tube ostia was also an important determinant of the directionality of flow. The lengths of the cervical os and fallopian tube ostia were of secondary importance in determining directionality of menstrual flow. CONCLUSION: If retrograde menstruation is a risk factor for the development of endometriosis, menstruating women with cervical os diameters less than 2.0 mm may be at increased risk for developing endometriosis.

Biomechanical Phenomena↗

PubMed1992

Generation and early differentiation of glial cells in the first optic ganglion of Drosophila melanogaster.

We have examined the generation and development of glial cells in the first optic ganglion, the lamina, of Drosophila melanogaster. Previous work has shown that the growth of retinal axons into the developing optic lobes induces the terminal cell divisions that generate the lamina monopolar neurons. We investigated whether photoreceptor ingrowth also influences the development of lamina glial cells, using P element enhancer trap lines, genetic mosaics and birthdating analysis. Enhancer trap lines that mark the differentiating lamina glial cells were found to require retinal innervation for expression. In mutants with only a few photoreceptors, only the few glial cells near ingrowing axons expressed the marker. Genetic mosaic analysis indicates that the lamina neurons and glial cells are readily separable, suggesting that these are derived from distinct lineages. Additionally, BrdU pulse-chase experiments showed that the cell divisions that produce lamina glia, unlike those producing lamina neurons, are not spatially or temporally correlated with the retinal axon ingrowth. Finally, in mutants lacking photoreceptors, cell divisions in the glial lineage appeared normal. We conclude that the lamina glial cells derive from a lineage that is distinct from that of the L-neurons, that glia are generated independently of photoreceptor input, and that completion of the terminal glial differentiation program depends, directly or indirectly, on an inductive signal from photoreceptor axons.

Animals↗

PubMed1990

Inhibition of renal electrolyte excretion by gabaergic pathways of the lateral hypothalamic area.

Injection of gamma amino butyric acid (GABA) into the lateral hypothalamic area of unrestrained conscious rats caused a decrease in renal electrolyte excretion with an increase in urinary flow. When picrotoxin, a specific inhibitor of gabaergic pathways, was administered, a significant increase in renal water and electrolyte excretion occurred. The effect of simultaneous injection of picrotoxin and GABA into the same site indicated that picrotoxin was less potent in reversing the effect induced by GABA than GABA was in reversing the effect of picrotoxin. We conclude that GABA acts directly on the neuronal mechanisms involved in the control of water and electrolyte excretion, perhaps by exerting a tonic inhibitory action on renal electrolyte excretion.

Animals↗

PubMed1990

Participation of opiate pathways in the lateral hypothalamic area in the control of renal electrolyte and water excretion.

Injection of Met-enkephalin (0.05, 0.25 and 0.50 micrograms in 1 microliter) solutions into the lateral hypothalamic area (LHA) of unrestrained and unanesthetized rats caused a significant decrease of sodium (0.39 +/- 0.13 to 0.07 +/- 0.01, P less than 0.05) and potassium (0.61 +/- 0.17 to 0.21 +/- 0.04, P less than 0.05) excretion. When the blocking agent naloxone (0.20 micrograms in 1 microliter) was injected alone, a significant increase of sodium (0.34 +/- 0.04 to 0.96 +/- 0.28, P less than 0.05) and potassium (0.76 +/- 0.13 to 1.72 +/- 0.30, P less than 0.05) excretion was observed. However, a dose-response relationship was not observed. However, when in another experiment naloxone was injected before Met-enkephalin into the same area, reversal of the effect of naloxone occurred, with decreased sodium and potassium excretion. We conclude that the enkephalinergic pathway of the LHA when stimulated with Met-enkephalin plays an inhibitory role in the control of sodium and potassium excretion.

Animals↗

PubMed1989

Characteristics of toad bladder urinary acidification.

1. The urinary acification system present in the bladder of the toad Bufo marinus ictericus was investigated by means of an improved technique of mounting the membrane that minimizes the edge damage when the bladder is placed as a sheet between lucite half chambers. 2. In ouabain-treated bladders in the absence of exogenous CO2, acidification rates were similar to those observed for turtle bladder. 3. The presence of 1% CO2 at the serosal gas phase increased proton secretion (JH). Stimulation of JH was also observed when the cell pH was decreased by back diffusion of salicylic acid added to the mucosal (M) compartment. 4. The estimate of the passive proton permeability of this epithelium as a whole yielded values around 1 x 10(-4) cm/s. The maximum pH gradient that could be established across the membrane in the short circuit condition (about 3 pH units) was taken as the apparent proton-motive force (PMF') of the system and these values were similar to those observed in the turtle bladder. 5. Luminal membrane depolarization caused by substitution of NaCl by KCl in Ringer solution led to an increase in JH at M pH = 7.3 without altering the PMF', which suggests that the electrical potential difference across the luminal membrane in ouabain-treated bladders is negligible when M pH is sufficiently acid to abolish H+ secretion.

Acid-Base Equilibrium↗

PubMed1984

Interaction between cholinergic and osmolar stimulation of the lateral hypothalamic area (LHA) on sodium and potassium excretion.

Hypotonic and isotonic solutions into the LHA of unrestrained rats caused no alteration in renal water and electrolyte excretion. Similar results were obtained after injecting hypo, iso and hypertonic glucose solutions. On the other hand, a hypertonic NaCl solution produced an increase in natriuresis and kaliuresis immediately after being injected into the LHA. The carbachol elicited an increase in natriuresis and kaliuresis as well as a decrease in urine output in the first urine samples collected after the injection being injected into the LHA. This response was not modified when the same dose of carbachol was injected associated with NaCl or glucose solutions. The observation of a lack of summation between the effects of carbachol and hypertonic NaCl, as well as the maintenance of the natriuretic and kaliuretic effects in response of the injection of the hypertonic solution even in the presence of blocked cholinergic pathways (atropine), suggests a dissociation between the mechanisms activated by the hypertonic solution and the cholinergic stimulation of the LHA.

Animals↗

PubMedDate not supplied

Changes in urinary electrolytes excretion after injections of ionic solutions into lateral hypothalamic area of rats.

Rats submitted to a chronically implanted cannula into lateral hypothalamic area (LHA) were utilized to study the effect of ionic stimulation of KCl, LiCl and CaCl2, sodium free solutions, on renal water and electrolyte excretion. In a general way decreases in natriuresis and kaliuresis following the injections of solutions into LHA were observed. Furthermore, significant increases in diuresis were noted after the injections of the 0.30 M solutions.

Animals↗