Publicaciones por año
Publicaciones del Departamento de Histología y Embriología
Gestational and Lactational Iron Deficiency Anemia Impairs Myelination and the Neurovascular Unit in Infant Rats
Mol Neurobiol 2022 59(6):3738-3754
Eugenia Isasi 1 2 , Martin Figares 2 3 , Verónica Abudara 3 , Silvia Olivera-Bravo 4
1 Neurobiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), 3318, Italia Av., 11600, Montevideo, Uruguay. 2 Neurobiología Celular y Molecular, Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Neurobiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), 3318, Italia Av., 11600, Montevideo, Uruguay. solivera2011@gmail.com.
DOI: 10.1007/s12035-022-02798-3
PMID: 35381889
Pubmed: https://pubmed.ncbi.nlm.nih.gov/35381889
Texto completo: https://dx.doi.org/10.1007/s12035-022-02798-3
Abstract:
Iron deficiency anemia is a prevalent health problem among pregnant women and infants, particularly in the developing countries that causes brain development deficits and poor cognitive outcomes. Since tissue iron depletion may impair myelination and trigger cellular hypoxic signaling affecting blood vessels, we studied myelination and the neurovascular unit (NVU) in infant rats born to mothers fed with an iron deficient (ID) or control diet from embryonic day 5 till weaning. Blood samples and brains of rat pups at postnatal day (PND) 14 and 30 were analyzed. PND 14 ID rats had severe microcytic hypochromic anemia that was almost reversed at PND 30 although hypomyelination and astrocyte immature phenotype in the corpus callosum were significant at that age. In CA1 hippocampal region, PND 14 and PND 30 ID rats showed significant reduced expression of the receptor β of the platelet-derived growth factor localized in pericytes and associated to aquaporin 4 (AQP4) immunopositive capillaries. Shorter AQP4 + capillaries and reduced AQP4 expression were also evidenced in PND 14 and PND 30 ID rats. In addition, pericyte membrane permeability through large-pore channels was transiently increased in ID rats at PND 14 but not at PND 30, while the blood-brain barrier permeability was not affected. Remarkably, transient increased pericyte permeability found in PND 14 ID rats was not directly related to iron depletion, suggesting the involvement of other iron deficiency anemia-induced mechanisms. In summary, severe ID during gestation and lactation produces persistent hypomyelination and significantly affects hippocampal pericytes and astrocytes in the NVU which may trigger impaired neurovascular function.
CD200R1 Contributes to Successful Functional Reinnervation after a Sciatic Nerve Injury
Cells 2022 11(11):1786
Bruno Pannunzio 1 2 , Jesús Amo-Aparicio 3 , Camila Julián 2 , Rubèn López-Vales 3 , Hugo Peluffo 1 2 4 , Natalia Lago 1 3
1 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay. 2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay. 3 Departament de Biologia Cel·lular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain. 4 Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, Catalonia, Spain.
DOI: 10.3390/cells11111786
PMID: 35681481
Pubmed: https://pubmed.ncbi.nlm.nih.gov/35681481
Texto completo: https://www.mdpi.com/resolver?pii=cells11111786
Abstract:
Activating and inhibitory immune receptors play a critical role in regulating systemic and central nervous system (CNS) immune and inflammatory processes. The CD200R1 immunoreceptor induces a restraining signal modulating inflammation and phagocytosis in the CNS under different inflammatory conditions. However, it remains unknown whether CD200R1 has a role in modulating the inflammatory response after a peripheral nerve injury, an essential component of the successful regeneration. Expression of CD200R1 and its ligand CD200 was analyzed during homeostasis and after a sciatic nerve crush injury in C57Bl/6 mice. The role of CD200R1 in Wallerian Degeneration (WD) and nerve regeneration was studied using a specific antibody against CD200R1 injected into the nerve at the time of injury. We found an upregulation of CD200R1 mRNA after injury whereas CD200 was downregulated acutely after nerve injury. Blockade of CD200R1 significantly reduced the acute entrance of both neutrophils and monocytes from blood after nerve injury. When long term regeneration and functional recovery were evaluated, we found that blockade of CD200R1 had a significant effect impairing the spontaneous functional recovery. Taken together, these results show that CD200R1 has a role in mounting a successful acute inflammatory reaction after injury, and contributes to an effective functional recovery.
Colocalization Analysis of Peripheral Myelin Protein-22 and Lamin-B1 in the Schwann Cell Nuclei of Wt and TrJ Mice
Biomolecules 2022 12(3):456
María Vittoria Di Tomaso 1 , Lucía Vázquez Alberdi 2 , Daniela Olsson 1 , Saira Cancela 1 , Anabel Fernández 3 4 , Juan Carlos Rosillo 3 5 , Ana Laura Reyes Ábalos 1 6 , Magdalena Álvarez Zabaleta 1 , Miguel Calero 7 8 , Alejandra Kun 2 9
1 Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay. 2 Laboratorio de Biología Celular del Sistema Nervioso Periférico, Departamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay. 3 Laboratorio de Neurobiología Comparada, Departamento de Neurociencias Integrativas, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay. 4 Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay. 5 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay. 6 Unidad de Microscopía Electrónica de Barrido, Universidad de la República, Montevideo 11400, Uruguay. 7 Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Unidad de Encefalopatías Espongiformes (UFIEC), 28029 Madrid, Spain. 8 Queen Sofia Foundation Alzheimer Center, CIEN Foundation, 28031 Madrid, Spain. 9 Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay.
DOI: 10.3390/biom12030456
PMID: 35327648
Pubmed: https://pubmed.ncbi.nlm.nih.gov/35327648
Texto completo: https://www.mdpi.com/resolver?pii=biom12030456
Abstract:
Myelination of the peripheral nervous system requires Schwann cells (SC) differentiation into the myelinating phenotype. The peripheral myelin protein-22 (PMP22) is an integral membrane glycoprotein, expressed in SC. It was initially described as a growth arrest-specific (gas3) gene product, up-regulated by serum starvation. PMP22 mutations were pathognomonic for human hereditary peripheral neuropathies, including the Charcot-Marie-Tooth disease (CMT). Trembler-J (TrJ) is a heterozygous mouse model carrying the same pmp22 point mutation as a CMT1E variant. Mutations in lamina genes have been related to a type of peripheral (CMT2B1) or central (autosomal dominant leukodystrophy) neuropathy. We explore the presence of PMP22 and Lamin B1 in Wt and TrJ SC nuclei of sciatic nerves and the colocalization of PMP22 concerning the silent heterochromatin (HC: DAPI-dark counterstaining), the transcriptionally active euchromatin (EC), and the nuclear lamina (H3K4m3 and Lamin B1 immunostaining, respectively). The results revealed that the number of TrJ SC nuclei in sciatic nerves was greater, and the SC volumes were smaller than those of Wt. The myelin protein PMP22 and Lamin B1 were detected in Wt and TrJ SC nuclei and predominantly in peripheral nuclear regions. The level of PMP22 was higher, and those of Lamin B1 lower in TrJ than in Wt mice. The level of PMP22 was higher, and those of Lamin B1 lower in TrJ than in Wt mice. PMP22 colocalized more with Lamin B1 and with the transcriptionally competent EC, than the silent HC with differences between Wt and TrJ genotypes. The results are discussed regarding the probable nuclear role of PMP22 and the relationship with TrJ neuropathy.
Neuroprotective effects of violacein in a model of inherited amyotrophic lateral sclerosis
Sci Rep 2022 12(1):4439
Silvia Olivera-Bravo 1 , Carmen Bolatto 2 3 , Gabriel Otero Damianovich 2 , Matías Stancov 2 , Sofía Cerri 2 3 , Paola Rodríguez 2 , Daniela Boragno 2 , Karina Hernández Mir 3 , María Noel Cuitiño 2 , Fernanda Larrambembere 2 , Eugenia Isasi 2 3 , Diego Alem 4 , Lucía Canclini 4 , Marta Marco 2 5 , Danilo Davyt 6 , Pablo Díaz-Amarilla 2
1 Cell and Mol Neurobiol Lab, NCIC Department, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. solivera@iibce.edu.uy. 2 Cell and Mol Neurobiol Lab, NCIC Department, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. 3 Histology and Embryology Department, Faculty of Medicine, Universidad de La República (UdelaR), Montevideo, Uruguay. 4 Genetic Department, IIBCE, Montevideo, Uruguay. 5 Tumoral Biol Area, Clin Biochem Department, Faculty of Chemistry, UdelaR, Montevideo, Uruguay. 6 Pharm Chem Lab, Organic Chemistry Department, Faculty of Chemistry, UdelaR, Montevideo, Uruguay.
DOI: 10.1038/s41598-022-06470-7
PMID: 35292673
Pubmed: https://pubmed.ncbi.nlm.nih.gov/35292673
Texto completo: https://doi.org/10.1038/s41598-022-06470-7
Abstract:
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive death of motor neurons and muscle atrophy, with defective neuron-glia interplay and emergence of aberrant glial phenotypes having a role in disease pathology. Here, we have studied if the pigment violacein with several reported protective/antiproliferative properties may control highly neurotoxic astrocytes (AbAs) obtained from spinal cord cultures of symptomatic hSOD1G93A rats, and if it could be neuroprotective in this ALS experimental model. At concentrations lower than those reported as protective, violacein selectively killed aberrant astrocytes. Treatment of hSOD1G93A rats with doses equivalent to the concentrations that killed AbAs caused a marginally significant delay in survival, partially preserved the body weight and soleus muscle mass and improved the integrity of the neuromuscular junction. Reduced motor neuron death and glial reactivity was also found and likely related to decreased inflammation and matrix metalloproteinase-2 and -9. Thus, in spite that new experimental designs aimed at extending the lifespan of hSOD1G93A rats are needed, improvements observed upon violacein treatment suggest a significant therapeutic potential that deserves further studies.
SIRT6 stabilization and cytoplasmic localization in macrophages regulates acute and chronic inflammation in mice
J Biol Chem 2022 298(3):101711
Mariana Bresque 1 , Karina Cal 2 , Valentina Pérez-Torrado 3 , Laura Colman 4 , Jorge Rodríguez-Duarte 5 , Cecilia Vilaseca 6 , Leonardo Santos 7 , María Pía Garat 7 , Santiago Ruiz 7 , Frances Evans 8 , Rosina Dapueto 1 , Paola Contreras 9 , Aldo Calliari 2 , Carlos Escande 10
1 Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay; Laboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay. 2 Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay; Departamento de Biociencias, Facultad de Veterinaria, Universidad de la República (UdelaR), Montevideo, Uruguay. 3 Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay; Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay; Área Inmunología, Departamento de Biociencias, Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay. 4 Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay; Departamento de Química Orgánica, Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay. 5 Laboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay. 6 Departamento de Fisiología, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay. 7 Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay. 8 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay; Laboratory of Neuroinflammation and Gene Therapy, Institut Pasteur Montevideo, Montevideo, Uruguay. 9 Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay; Departamento de Fisiología, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay. 10 Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay. Electronic address: escande@pasteur.edu.uy.
DOI: 10.1016/j.jbc.2022.101711
PMID: 35150745
Pubmed: https://pubmed.ncbi.nlm.nih.gov/35150745
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(22)00151-X
Abstract:
Acute and chronic inflammations are key homeostatic events in health and disease. Sirtuins (SIRTs), a family of NAD-dependent protein deacylases, play a pivotal role in the regulation of these inflammatory responses. Indeed, SIRTs have anti-inflammatory effects through a myriad of signaling cascades, including histone deacetylation and gene silencing, p65/RelA deacetylation and inactivation, and nucleotide‑binding oligomerization domain, leucine rich repeat, and pyrin domain‑containing protein 3 inflammasome inhibition. Nevertheless, recent findings show that SIRTs, specifically SIRT6, are also necessary for mounting an active inflammatory response in macrophages. SIRT6 has been shown to positively regulate tumor necrosis factor alpha (TNFα) secretion by demyristoylating pro-TNFα in the cytoplasm. However, how SIRT6, a nuclear chromatin-binding protein, fulfills this function in the cytoplasm is currently unknown. Herein, we show by Western blot and immunofluorescence that in macrophages and fibroblasts there is a subpopulation of SIRT6 that is highly unstable and quickly degraded via the proteasome. Upon lipopolysaccharide stimulation in Raw 264.7, bone marrow, and peritoneal macrophages, this population of SIRT6 is rapidly stabilized and localizes in the cytoplasm, specifically in the vicinity of the endoplasmic reticulum, promoting TNFα secretion. Furthermore, we also found that acute SIRT6 inhibition dampens TNFα secretion both in vitro and in vivo, decreasing lipopolysaccharide-induced septic shock. Finally, we tested SIRT6 relevance in systemic inflammation using an obesity-induced chronic inflammatory in vivo model, where TNFα plays a key role, and we show that short-term genetic deletion of SIRT6 in macrophages of obese mice ameliorated systemic inflammation and hyperglycemia, suggesting that SIRT6 plays an active role in inflammation-mediated glucose intolerance during obesity.
Pathophysiological and molecular considerations of viral and bacterial infections during maternal-fetal and -neonatal interactions of SARS-CoV-2, Zika, and Mycoplasma infectious diseases
Biochim Biophys Acta Mol Basis Dis 2022 1868(1):166285
Gonzalo Ferreira 1 , Fernanda Blasina 2 , Marianela Rodríguez Rey 2 , Gabriel Anesetti 3 , Rosana Sapiro 3 , Luisina Chavarría 4 , Romina Cardozo 4 , Grazzia Rey 5 , Luis Sobrevia 6 , Garth L Nicolson 7
1 Laboratory of Ion Channels, Biological Membranes and Cell Signaling, Dept. of Biophysics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay. Electronic address: ferreira@fmed.edu.uy. 2 Dept. of Neonatology, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay. 3 Dept. of Histology and Development, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay. 4 Laboratory of Ion Channels, Biological Membranes and Cell Signaling, Dept. of Biophysics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay. 5 Dept. of Clinical Ginecology and Obstetrics B, Facultad de Medicina, Universidad de la Republica, Uruguay. 6 Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-41012, Spain; Medical School, Faculty of Medicine, Sao Paulo State University (UNESP), Brazil; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Australia; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713GZ Groningen, The Netherlands. 7 Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, CA, USA.
DOI: 10.1016/j.bbadis.2021.166285
PMID: 34624499
Pubmed: https://pubmed.ncbi.nlm.nih.gov/34624499
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0925-4439(21)00218-0
Abstract:
During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level.
Pericyte Mapping in Cerebral Slices with the Far-red Fluorophore TO-PRO-3
Bio Protoc 2021 11(22):e4222
Sandra P Mai-Morente 1 , Juan P Irigoyen 1 , Victoria M Carriquiry 1 , Virginia M Marset 1 , Mariana Di Doménico 2 , Eugenia Isasi 3 , Verónica Abudara 1
1 Departamento de Fisiología, Facultad de Medicina, Universidad de la República, General Flores 2125, Montevideo, CP 11 800, Uruguay. 2 Departamento de Biofísica, Facultad de Medicina, Universidad de la República, General Flores 2125, Montevideo, CP 11 800, Uruguay. 3 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, General Flores 2125, Montevideo, CP 11 800, Uruguay.
DOI: 10.21769/BioProtoc.4222
PMID: 34909443
Pubmed: https://pubmed.ncbi.nlm.nih.gov/34909443
Texto completo: https://bio-protocol.org/e4222
Abstract:
This protocol describes a method for high-resolution confocal imaging of pericytes with the far-red fluorophore TO-PROTM-3 Iodide 642/661 in cerebral slices of murine. Identification of pericytes with TO-PRO-3 is a short time-consuming, high cost-effective and robust technique to label pericytes with no need for immunostaining or generation of reporter mice. Since the TO-PRO-3 stain resists immunofluorescence, and lacks spectral overlap, the probe is well suited for multiple labelling. Our procedures also combine TO-PRO-3-staining of pericytes with fluorescent markers for astrocytes and vessels in brain slices. These approaches should enable the assessment of pericyte biology in gliovascular unit.
Increased mitochondrial activity upon CatSper channel activation is required for mouse sperm capacitation
Redox Biol 2021 48:102176
Juan J Ferreira 1 , Adriana Cassina 2 , Pilar Irigoyen 3 , Mariana Ford 3 , Santiago Pietroroia 3 , Nikita Peramsetty 1 , Rafael Radi 2 , Celia M Santi 4 , Rossana Sapiro 5
1 Department of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, St. Louis, MO, United States; Department of Neuroscience, Washington University in St. Louis, School of Medicine, St. Louis, MO, United States. 2 Departamento de Bioquímica and Centro de Investigaciones Biomédicas (CEINBIO) Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 Departamento de Histología y Embriología and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina UDELAR, Montevideo, Uruguay. 4 Department of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University in St. Louis, School of Medicine, St. Louis, MO, United States; Department of Neuroscience, Washington University in St. Louis, School of Medicine, St. Louis, MO, United States. Electronic address: Santic@wustl.edu. 5 Departamento de Histología y Embriología and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina UDELAR, Montevideo, Uruguay. Electronic address: rsapiro@fmed.edu.uy.
DOI: 10.1016/j.redox.2021.102176
PMID: 34753004
Pubmed: https://pubmed.ncbi.nlm.nih.gov/34753004
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S2213-2317(21)00336-0
Abstract:
To fertilize an oocyte, sperm must undergo several biochemical and functional changes known as capacitation. A key event in capacitation is calcium influx through the cation channel of sperm (CatSper). However, the molecular mechanisms of capacitation downstream of this calcium influx are not completely understood. Capacitation is also associated with an increase in mitochondrial oxygen consumption, and several lines of evidence indicate that regulated calcium entry into mitochondria increases the efficiency of oxidative respiration. Thus, we hypothesized that calcium influx through CatSper during capacitation increases mitochondrial calcium concentration and mitochondrial efficiency and thereby contributes to sperm hyperactivation and fertilization capacity. To test this hypothesis, we used high-resolution respirometry to measure mouse sperm mitochondrial activity. We also measured mitochondrial membrane potential, ATP/ADP exchange during capacitation, and mitochondrial calcium concentration in sperm from wild-type and CatSper knockout mice. We show that the increase in mitochondrial activity in capacitated wild-type sperm parallels the increase in mitochondrial calcium concentration. This effect is blunted in sperm from CatSper knockout mice. Importantly, these mechanisms are needed for optimal hyperactivation and fertilization in wild-type mice, as confirmed by using mitochondrial inhibitors. Thus, we describe a novel mechanism of sperm capacitation. This work contributes to our understanding of the role of mitochondria in sperm physiology and opens the possibility of new molecular targets for fertility treatments and male contraception.
Immunohistochemical description of isotocin neurons and the anatomo-functional comparative analysis between isotocin and vasotocin systems in the weakly electric fish, Gymnotus omaroum
Gen Comp Endocrinol 2021 313:113886
Paula Pouso 1 , Rossana Perrone 2 , Ana Silva 3
1 Depto. Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Unidad Bases Neurales de la Conducta, Depto Neurofisiologia Celular y Molecular, IIBCE, Montevideo, Uruguay. Electronic address: ppouso@fmed.edu.uy. 2 Unidad Bases Neurales de la Conducta, Depto Neurofisiologia Celular y Molecular, IIBCE, Montevideo, Uruguay; Instituto de Fundamentos y Métodos, Facultad de Psicología, Universidad de la República. 3 Unidad Bases Neurales de la Conducta, Depto Neurofisiologia Celular y Molecular, IIBCE, Montevideo, Uruguay; Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
DOI: 10.1016/j.ygcen.2021.113886
PMID: 34411583
Pubmed: https://pubmed.ncbi.nlm.nih.gov/34411583
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0016-6480(21)00179-9
Abstract:
The vasopressin-vasotocin (AVP-AVT) and oxytocin-mesotocin-isotocin (OT-MT-IT) families of nonapeptides are of great importance in shaping context-dependent modulations of a conserved and yet highly plastic network of brain areas involved in social behavior: the social behavior network. The nonapeptide systems of teleost fish are highly conserved and share a common general organization. In this study, we first describe the presence of IT cells and projections in the brain of an electric fish, Gymnotus omarorum. Second, we confirm that IT neuron types and distribution in the preoptic area (POA) follow the same general pattern previously described in other teleost species. Third, we show that although IT and AVT neurons occur intermingled within the POA of G. omarorum and can be classified into the same subgroups, they present subtle but remarkable differences in size, number, and location. Finally, we show that unlike AVT, IT has no effect on basal electric signaling, reinforcing the specificity in the actions that each one of these nonapeptides has on social behavior and communication.
Functional expression of P2Y2 receptors in mouse ovarian surface epithelium (OSE)
Mol Reprod Dev 2021 88(11):758-770
Ana Patricia Juárez-Mercado 1 , Rebeca Chávez-Genaro 2 , Tatiana Fiordelisio 3 , Adriana González-Gallardo 1 , Mauricio Díaz-Muñoz 1 , Francisco G Vázquez-Cuevas 1
1 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México. 2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 Laboratorio de Neuroendocrinología Comparada, Departamento de Ecología y Recursos Naturales, Biología, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad Universitaria, CDMX, México.
DOI: 10.1002/mrd.23545
PMID: 34694051
Pubmed: https://pubmed.ncbi.nlm.nih.gov/34694051
Texto completo: https://doi.org/10.1002/mrd.23545
Abstract:
Ovarian surface epithelium (OSE) is a cell monolayer surrounding the ovary; it is involved in the regulation of the ovulatory process and the genesis of ovarian carcinoma. However, intercellular messengers regulating signaling events, like proliferation in the OSE, have not been completely described. Purines have emerged as novel intercellular messengers in the ovary, in which expression of purinergic receptors has been reported in different cell types. In the present work, we described the functional expression of P2Y2 receptor (P2Y2R), a purinergic receptor widely associated with cell proliferation, in the OSE. The expression of P2Y2R by immunofluorescence and RT-PCR, and its functionality by Ca2+ recording was demonstrated in primary cultured OSE. Functional expression of P2Y2R was also exhibited in situ, by recording of intracellular Ca2+ release and detection of ERK phosphorylation after injection of a selective agonist into the ovarian bursa. Furthermore, P2Y2R activation with UTPγS, in situ, induced cell proliferation at 24 h, whereas continuous stimulation of P2Y2R during a complete estrous cycle significantly modified the size distribution of the follicular population. This is the first evidence of the functional expression of purinergic P2Y2R in the OSE and opens new perspectives on the roles played by purines in ovarian physiology.