Publicaciones por año
Publicaciones del Departamento de Histología y Embriología
Sensory processing in the fast electrosensory pathway of pulse gymnotids studied at multiple integrative levels
Comp Biochem Physiol A Mol Integr Physiol 2008 Nov;151(3):370-380
María E Castelló 1 , Javier Nogueira 1 , Omar Trujillo-Cenóz 2 , Angel A Caputi 3
1 Departamento de Neurociencias Integrativas y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable, Unidad Asociada de la Facultad de Ciencias, Universidad de la República. Montevideo, Av Italia 3318, 11600, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República. Montevideo, Uruguay. 2 Departamento de Neuroanatomía Comparada, Instituto de Investigaciones Biológicas Clemente Estable, Unidad Asociada de la Facultad de Ciencias, Universidad de la República. Montevideo, Uruguay. 3 Departamento de Neurociencias Integrativas y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable, Unidad Asociada de la Facultad de Ciencias, Universidad de la República. Montevideo, Av Italia 3318, 11600, Uruguay. Electronic address: angel@iibce.edu.uy.
DOI: 10.1016/j.cbpa.2007.04.012
PMID: 17513149
Pubmed: https://pubmed.ncbi.nlm.nih.gov/17513149
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S1095-6433(07)00988-9
Abstract:
Pulse gymnotids extract information about the environment using the pulsed discharge of an electric organ. Cutaneous electroreceptor organs transduce and encode the changes that objects imprint on the self-generated transcutaneous electric field. This review deals with the role of a neural circuit, the fast electrosensory path of pulse gymnotids, in the streaming of self generated electrosensory signals. The activation of this path triggers a low-responsiveness window slightly shorter than the interval between electric organ discharges. This phenomenon occurs at the electrosensory lateral line lobe where primary afferent terminals project on the somata of spherical neurons. The main subservient mechanism of the low-responsiveness window rely on the intrinsic properties of spherical neurons (dominated by a voltage dependent, low-threshold, non-inactivating and slowly-deactivating K(+) conductance) determining the cell to respond with a single spike followed by a long refractory period. Externally generated signals that randomly occur within the interval between self-generated discharges are likely blocked by the low responsiveness window. Repetitive signals, as those emitted by conspecifics with a slightly lower rate, occur progressively at longer delays beyond the duration of the low responsiveness window. Transient increases of the discharge rate relocate the interference within the low-responsiveness window. We propose that this combination of sensory filtering and electromotor control favors the self-generated signals in detriment of other, securing the continuity of the electrolocation stream.
Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification
Free Radic Biol Med 2008 Sep 15;45(6):733-42
Florencia Irigoín 1 3, Lucía Cibils 2 3, Marcelo A Comini 4, Shane R Wilkinson 5, Leopold Flohé 6, Rafael Radi 2 3
1 Departmento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Uruguay 2 Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Uruguay 3 Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Uruguay 4 Biochemie-Zentrum der Universität Heidelberg, 69120 Heidelberg, Germany 5 School of Biological and Chemical Sciences, Queen Mary University of London, London, UK 6 MOLISA GmbH, 39118 Magdeburg, Germany
DOI: 10.1016/j.freeradbiomed.2008.05.028
PMID: 18588970
Pubmed: https://pubmed.ncbi.nlm.nih.gov/18588970
Texto completo: https://www.sciencedirect.com/science/article/abs/pii/S089158490800347X?via%3Dihub
Abstract:
Trypanosoma cruzi is the etiologic agent of Chagas' disease, an infection that affects several million people in Latin America. With no immediate prospect of a vaccine and problems associated with current chemotherapies, the development of new treatments is an urgent priority. Several aspects of the redox metabolism of this parasite differ enough from those in the mammalian host to be considered targets for drug development. Here, we review the information about a trypanosomatid-specific molecule centrally involved in redox metabolism, the dithiol trypanothione, and the main effectors of cellular antioxidant defense. We focus mainly on data from T. cruzi, making comparisons with other trypanosomatids whenever possible. In these parasites trypanothione participates in crucial thiol-disulfide exchange reactions and serves as electron donor in different metabolic pathways, from synthesis of DNA precursors to oxidant detoxification. Interestingly, the levels of several enzymes involved in trypanothione metabolism and oxidant detoxification increase during the transformation of T. cruzi to its mammalian-infective form and the overexpression of some of them has been associated with increased resistance to macrophage-dependent oxidative killing. Together, the evidence suggests a central role of the trypanothione-dependent antioxidant systems in the infection process.
Toll receptor 4 Asp299Gly polymorphism and its association with preterm birth and premature rupture of membranes in a South American population
Mol Hum Reprod 2008 Sep;14(9):555-9
G Rey 1, F Skowronek 1, J Alciaturi 1, J Alonso 2, B Bertoni 3, R Sapiro 1 4
1 Laboratory of Molecular Biology of Reproduction, Department of Histology and Embryology, School of Medicine, Gral. Flores 2125, CP 11800 Montevideo, Uruguay 2 Department of Obstetrics and Gynecology, C Pereira Rossell Hospital, School of Medicine, University of Uruguay, Montevideo, Uruguay 3 Department of Genetics, School of Medicine, University of Uruguay, Montevideo, Uruguay 4 Correspondence address. Tel: +598-2924-3414; E-mail: rsapiro@fmed.edu.uy
DOI: 10.1093/molehr/gan049
PMID: 18723631
Pubmed: https://pubmed.ncbi.nlm.nih.gov/18723631
Texto completo: https://academic.oup.com/molehr/article-lookup/doi/10.1093/molehr/gan049
Abstract:
Preterm birth (PTB) is a worldwide health problem and remains the leading cause of perinatal morbidity and mortality. Systemic and local intrauterine infections have been implicated in the pathogenesis of preterm labor and delivery. Common pathways between PTB, premature rupture of ovular membranes (PROM) and altered molecular routes of inflammation have been proposed. There is evidence to support a genetic component in these conditions. Lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, is thought to play a key role in eliciting an inflammatory response. LPS is recognized by proteins of the innate immune system, including Toll-like receptor 4 (TLR4). Individuals from some European countries carrying the variant alleles resulting in an amino acid substitution (Asp299Gly) are at increased risk of Gram-negative infections and premature birth. The objective of this study was to determine if preterm newborns have different allele frequency of the Asp299Gly TLR4 variant from healthy term neonates in Uruguay. The impact of PROM was also examined. There was an increase in the risk for fetuses carrying the Asp299Gly substitution in TLR4 of being severely premature (<33 weeks) and to present PROM at the same time.
Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants
J Neurosci 2008 Apr 16;28(16):4115-22
Patricia Cassina 1 3, Adriana Cassina 2 3, Mariana Pehar 4, Raquel Castellanos 1, Mandi Gandelman 1 5, Andrés de León 1 5, Kristine M Robinson 7, Ronald P Mason 6, Joseph S Beckman 7, Luis Barbeito 3 4 5, Rafael Radi 2 3
1 Departamento de Histología, 2 Departamento de Bioquímica, and 3 Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, 11800 Montevideo, Uruguay, 4 Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, Uruguay, 5 Neurodegeneration Laboratory, Institut Pasteur, 11400 Montevideo, Uruguay, 6 Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, North Carolina 27709, and 7 Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331
DOI: .1523/JNEUROSCI.5308-07.2008
PMID: 18417691
Pubmed: https://pubmed.ncbi.nlm.nih.gov/18417691
Texto completo: https://www.jneurosci.org/content/28/16/4115
Abstract:
Mitochondrial dysfunction and oxidative stress contribute to motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Recent reports indicate that astrocytes expressing the mutations of superoxide dismutase-1 (SOD1) may contribute to motor neuron injury in ALS. Here, we provide evidence that mitochondrial dysfunction in SOD1(G93A) rat astrocytes causes astrocytes to induce apoptosis of motor neurons. Mitochondria from SOD1(G93A) rat astrocytes displayed a defective respiratory function, including decreased oxygen consumption, lack of ADP-dependent respiratory control, and decreased membrane potential. Protein 3-nitrotyrosine was detected immunochemically in mitochondrial proteins from SOD1(G93A) astrocytes, suggesting that mitochondrial defects were associated with nitroxidative damage. Furthermore, superoxide radical formation in mitochondria was increased in SOD1(G93A) astrocytes. Similar defects were found in mitochondria isolated from the spinal cord of SOD1(G93A) rats, and pretreatment of animals with the spin trap 5,5-dimethyl-1-pyrroline N-oxide restored mitochondrial function, forming adducts with mitochondrial proteins in vivo. As shown previously, SOD1(G93A) astrocytes induced death of motor neurons in cocultures, compared with nontransgenic ones. This behavior was recapitulated when nontransgenic astrocytes were treated with mitochondrial inhibitors. Remarkably, motor neuron loss was prevented by preincubation of SOD1(G93A) astrocytes with antioxidants and nitric oxide synthase inhibitors. In particular, low concentrations (approximately 10 nm) of two mitochondrial-targeted antioxidants, ubiquinone and carboxy-proxyl nitroxide, each covalently coupled to a triphenylphosphonium cation (Mito-Q and Mito-CP, respectively), prevented mitochondrial dysfunction, reduced superoxide production in SOD1(G93A) astrocytes, and restored motor neuron survival. Together, our results indicate that mitochondrial dysfunction in astrocytes critically influences motor neuron survival and support the potential pharmacological utility of mitochondrial-targeted antioxidants in ALS treatment.
Echinococcus granulosus: the establishment of the metacestode is associated with control of complement-mediated early inflammation
Exp Parasitol 2008 Feb;118(2):188-96
Martin Breijo 1 2, Gabriel Anesetti 3, Laura Martínez 3, Robert B Sim 4, Ana M Ferreira 2
1 Departamento de Ciencias Microbiológicas, Area Inmunología, Facultad de Veterinaria, Universidad de la República, A. Lasplaces 1620, Montevideo CP11600, Uruguay 2 Cátedra de Inmunología, Facultad de Ciencias/Facultad de Química, Universidad de la República, Instituto de Higiene, Avda A. Navarro 3051, p2, Montevideo CP 11600, Uruguay 3 Departamento de Histología, Facultad de Veterinaria, Universidad de la República, A. Lasplaces 1620, Montevideo CP11600, Uruguay 4 MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
DOI: 10.1016/j.exppara.2007.07.014
PMID: 17905232
Pubmed: https://pubmed.ncbi.nlm.nih.gov/17905232
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0014-4894(07)00205-6
Abstract:
In this work we studied the evolution of early inflammation, complement activation and parasite survival/death along the establishment phase of Echinococcus granulosus metacestode. Using a chamber model of infection in mice, we examined cell infiltration and C3 deposition on individual parasites during their development from protoscoleces to cystic forms. We found that the intensity of the initial inflammation decreased around undamaged but not around damaged parasites: at 43dpi undamaged parasites were mostly associated with poor/mild inflammation while damaged parasites with a strong inflammation. In addition, whereas complement activation participated in the induction of early inflammation, the deposition of C3 on undamaged parasites progressively diminished. Interestingly, we observed some parasites in pre-cystic stage with no/poor C3 deposition at 3dpi. Overall, these results indicated that the establishment and survival of the hydatid cyst is associated with the control of complement and, consequently, of local inflammation at the initial phases of infection.
Sympathetic pharmacological denervation in ageing rats: effects on ovulatory response and follicular population
Reprod Fertil Dev 2007 19(8):954-60
Rebeca Chávez-Genaro 1 4, Paula Lombide 1 2, Roberto Domínguez 3, Patricia Rosas 3, Francisco Vázquez-Cuevas 3
1 Histology and Embryology Department, School of Medicine, General Flores 2125, CP 11800, Montevideo, Uruguay. 2 Cell Biology Section, Sciences Faculty, Iguá 4225, CP 11400, Montevideo, Uruguay. 3 Biology of Reproduction Research Unit, Laboratory of Reproductive Physiology, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, AP 9-020, CP 15000, México, D. F. México. 4 Corresponding author. Email: rchavez@fmed.edu.uy
DOI: 10.1071/rd07075
PMID: 18076827
Pubmed: https://pubmed.ncbi.nlm.nih.gov/18076827
Texto completo: https://www.publish.csiro.au/RD/RD07075
Abstract:
The present study analyses the participation of ovarian innervation during reproductive senescence. We use the model of acute peripheral pharmacological sympathetic denervation with guanethidine in young (3 months old), middle-aged (12 months old) or old (18 months old) rats with spontaneous or induced ovulation. Ovarian levels of norepinephrine (NE) were measured by HPLC and the oestrous cycle, the number of ovulating animals and the percentage of atretic follicles were also assessed. Aged animals showed a progressive reduction in ovulatory capacity and an increase in ovarian NE content. Acute denervation increased the percentage of healthy follicles in 12- and 18-month-old rats compared with control adult animals. Combined treatment of denervation plus stimulation with gonadotrophins doubled the number of ova shed in young adult rats and restablished a partial ovulation in 12-month-old rats. The results suggest that ovarian noradrenergic innervation plays a modulator role in ovarian physiology during the ageing ovary process. The action of ovarian noradrenergic innervation seems to be associated with folliculogenesis and the ovarian response to gonadotrophins.
A quantitative study of rat uterine sympathetic innervation during pregnancy and post partum
Reprod Fertil Dev 2006 2006;18(5):525-31
R Chávez-Genaro 1 4, P Lombide 1 2, G Anesetti 1 3
1 Departamento de Histología y Embriología, Facultad de Medicina, General Flores 2125, CP 11800, Montevideo, Uruguay. 2 Sección Biología Celular, Departamento de Biología Celular y Molecular, Instituto de Biología, Facultad de Ciencias, Iguá 4245, CP 11400, Montevideo, Uruguay. 3 Area de Histología y Embriología, Facultad de Veterinaria, Las Places 1550, CP 11600, Montevideo, Uruguay. 4 Corresponding author. Email: rchavez@fmed.edu.uy
DOI: 10.1071/rd05053
PMID: 16836959
Pubmed: https://pubmed.ncbi.nlm.nih.gov/16836959
Texto completo: https://www.publish.csiro.au/rd/RD05053
Abstract:
In mammals, pregnancy induces a transient and extensive degeneration of uterine sympathetic innervation. We used the models of unilateral oviduct ligation and in oculo myometrium transplant in pregnant rats to address the role of stretching forces and/or hormone milieu in the loss of sympathetic innervation. The sympathetic fibres of the uterine horn and in oculo myometrial transplants were quantified on tissue sections processed by the glyoxylic acid technique. In normal pregnant rats, the density of uterine horn innervation was significantly reduced at late pregnancy and recovery took place during post partum. The empty horn of pregnant rats showed no significant changes in density of myometrial innervation during pregnancy or post partum. In oculo myometrial transplants were organotypically reinnervated in virgin animals. When the transplants were exposed to gestational hormonal milieu, few or no fibres were observed to the end of pregnancy; however, a significant increase at post partum was observed. Results showed that both the effects of stretching and the hormone milieu derived from the fetus-placenta complex play a role as inductors of changes on sympathetic myometrial innervation during pregnancy and support the idea that immature muscular uterine fibres are more susceptible to the effects of pregnancy than those originating from adult animals.
Fibroblast growth factor-1 induces heme oxygenase-1 via nuclear factor erythroid 2-related factor 2 (Nrf2) in spinal cord astrocytes: consequences for motor neuron survival
J Biol Chem 2005 Jul 8;280(27):25571-9
Marcelo R Vargas 1, Mariana Pehar 1, Patricia Cassina 2, Laura Martínez-Palma 2, John A Thompson 3, Joseph S Beckman 4, Luis Barbeito 1
1 Departamento de NeurobiologíaCelular y Molecular, Instituto de Investigaciones Biológicas ClementeEstable, Montevideo 11600, Uruguay, the 2 Departamento de Histología, Facultad deMedicina, Universidad de la República, Montevideo 11800, Uruguay, the 3 Department of Surgery, University of Alabama atBirmingham, Birmingham, Alabama 35294, and the 4 Linus Pauling Institute, Environmental HealthSciences Center, Department of Biochemistry and Biophysics, Oregon StateUniversity, Corvallis, Oregon 97331
DOI: 10.1074/jbc.M501920200
PMID: 15870071
Pubmed: https://pubmed.ncbi.nlm.nih.gov/15870071
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)61369-2
Abstract:
Fibroblast growth factor-1 (FGF-1) is highly expressed in motor neurons and can be released in response to sublethal cell injury. Because FGF-1 potently activates astroglia and exerts a direct neuroprotection after spinal cord injury or axotomy, we examined whether it regulated the expression of inducible and cytoprotective heme oxygenase-1 (HO-1) enzyme in astrocytes. FGF-1 induced the expression of HO-1 in cultured rat spinal cord astrocytes, which was dependent on FGF receptor activation and prevented by cycloheximide. FGF-1 also induced Nrf2 mRNA and protein levels and prompted its nuclear translocation. HO-1 induction was abolished by transfection of astrocytes with a dominant-negative mutant Nrf2, indicating that FGF-1 regulates HO-1 expression through Nrf2. FGF-1 also modified the expression of other antioxidant genes regulated by Nrf2. Both Nrf2 and HO-1 levels were increased and co-localized with reactive astrocytes in the degenerating lumbar spinal cord of rats expressing the amyotrophic lateral sclerosis-linked SOD1 G93A mutation. Overexpression of Nrf2 in astrocytes increased survival of co-cultured embryonic motor neurons and prevented motor neuron apoptosis mediated by nerve growth factor through p75 neurotrophin receptor. Taken together, these results emphasize the key role of astrocytes in determining motor neuron fate in amyotrophic lateral sclerosis.
Astrocyte activation by fibroblast growth factor-1 and motor neuron apoptosis: implications for amyotrophic lateral sclerosis
J Neurochem 2005 Apr;93(1):38-46
Patricia Cassina 1, Mariana Pehar 1 2, Marcelo R Vargas 2, Raquel Castellanos 1, Ana G Barbeito 1, Alvaro G Estévez 3, John A Thompson 4, Joseph S Beckman 5, Luis Barbeito 2
1 Departamento de Histología, Facultad de Medicina, Universidad de la República Montevideo, Uruguay 2 Departamento de Neurobiología Celular, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay 3 Department of Physiology and Biophysics and 4 Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA 5 Linus Pauling Institute, Environmental Health Sciences Center, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA
DOI: 10.1111/j.1471-4159.2004.02984.x
PMID: 15773903
Pubmed: https://pubmed.ncbi.nlm.nih.gov/15773903
Texto completo: https://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2004.02984.x
Abstract:
Fibroblast growth factor-1 (FGF1 or acidic FGF) is highly expressed in motor neurons. FGF-1 is released from cells by oxidative stress, which might occur from SOD-1 aberrant function in amyotrophic lateral sclerosis (ALS). Although FGF-1 is known to be neuroprotective after spinal cord injury or axotomy, we found that FGF-1 could activate spinal cord astrocytes in a manner that decreased motor neuron survival in co-cultures. FGF-1 induced accumulation of the FGF receptor 1 (FGFR1) in astrocyte nuclei and potently stimulated nerve growth factor (NGF) expression and secretion. The FGFR1 tyrosine kinase inhibitor PD166866 prevented these effects. Previously, we have shown that NGF secretion by reactive astrocytes induces motor neuron apoptosis through a p75(NTR)-dependent mechanism. Embryonic motor neurons co-cultured on the top of astrocytes exhibiting activated FGFR1 underwent apoptosis, which was prevented by PD166866 or by adding either anti-NGF or anti-p75(NTR) neutralizing antibodies. In the degenerating spinal cord of mice carrying the ALS mutation G93A of Cu, Zn superoxide dismutase, FGF-1 was no longer localized only in the cytosol of motor neurons, while FGFR1 accumulated in the nuclei of reactive astrocytes. These results suggest that FGF-1 released by oxidative stress from motor neurons might have a role in activating astrocytes, which could in turn initiate motor neuron apoptosis in ALS through a p75(NTR)-dependent mechanism.
A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis
Brain Res Brain Res Rev 2004 Dec;47(1-3):263-74
Luis H Barbeito 1, Mariana Pehar 1 2, Patricia Cassina 2, Marcelo R Vargas 1, Hugo Peluffo 2, Liliana Viera 3, Alvaro G Estévez 3, Joseph S Beckman 4
1 Departamento de Neurobiologı́a Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318-CP 11600, Montevideo, Uruguay 2 Departamento de Histologı́a y Embriologı́a, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 3 Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL, USA 4 Linus Pauling Institute, Environmental Health Sciences Center, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA
DOI: 10.1016/j.brainresrev.2004.05.003
PMID: 15572176
Pubmed: https://pubmed.ncbi.nlm.nih.gov/15572176
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0165017304000700
Abstract:
A strong glial reaction typically surrounds the affected upper and lower motor neurons and degenerating descending tracts of ALS patients. Reactive astrocytes in ALS contain protein inclusions, express inflammatory makers such as the inducible forms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), display nitrotyrosine immunoreactivity and downregulate the glutamate transporter EAAT2. In this review, we discuss the evidence sustaining an active role for astrocytes in the induction and propagation of motor neuron loss in ALS. Available evidence supports the view that glial activation could be initiated by proinflammatory mediators secreted by motor neurons in response to injury, axotomy or muscular pathology. In turn, reactive astrocytes produce nitric oxide and peroxynitrite, which cause mitochondrial damage in cultured neurons and trigger apoptosis in motor neurons. Astrocytes may also contribute to the excitotoxic damage of motor neurons by decreasing glutamate transport or actively releasing the excitotoxic amino acid. In addition, reactive astrocytes secrete pro-apoptotic mediators, such as nerve growth factor (NGF) or Fas-ligand, a mechanism that may serve to eliminate vulnerable motor neurons. The comprehensive understanding of the interactions between motor neurons and glia in ALS may lead to a more accurate theory of the pathogenesis of the disease.