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Publicaciones del Departamento de Histología y Embriología
Pyruvate dehydrogenase kinase 2 knockdown restores the ability of amyotrophic lateral sclerosis-linked SOD1G93A rat astrocytes to support motor neuron survival by increasing mitochondrial respiration
Glia 2024 May;72(5):999-1011
Ernesto Miquel 1 , Rosalía Villarino 1 , Laura Martínez-Palma 1 , Adriana Cassina 2 , Patricia Cassina 1
1 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 2 Departamento de Bioquímica, Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
DOI: 10.1002/glia.24516
PMID: 38372421
Pubmed: https://pubmed.ncbi.nlm.nih.gov/38372421
Texto completo: https://doi.org/10.1002/glia.24516
Abstract:
Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron (MN) degeneration. Various studies using cellular and animal models of ALS indicate that there is a complex interplay between MN and neighboring non-neuronal cells, such as astrocytes, resulting in noncell autonomous neurodegeneration. Astrocytes in ALS exhibit a lower ability to support MN survival than nondisease-associated ones, which is strongly correlated with low-mitochondrial respiratory activity. Indeed, pharmacological inhibition of pyruvate dehydrogenase kinase (PDK) led to an increase in the mitochondrial oxidative phosphorylation pathway as the primary source of cell energy in SOD1G93A astrocytes and restored the survival of MN. Among the four PDK isoforms, PDK2 is ubiquitously expressed in astrocytes and presents low expression levels in neurons. Herein, we hypothesize whether selective knockdown of PDK2 in astrocytes may increase mitochondrial activity and, in turn, reduce SOD1G93A-associated toxicity. To assess this, cultured neonatal SOD1G93A rat astrocytes were incubated with specific PDK2 siRNA. This treatment resulted in a reduction of the enzyme expression with a concomitant decrease in the phosphorylation rate of the pyruvate dehydrogenase complex. In addition, PDK2-silenced SOD1G93A astrocytes exhibited restored mitochondrial bioenergetics parameters, adopting a more complex mitochondrial network. This treatment also decreased lipid droplet content in SOD1G93A astrocytes, suggesting a switch in energetic metabolism. Significantly, PDK2 knockdown increased the ability of SOD1G93A astrocytes to support MN survival, further supporting the major role of astrocyte mitochondrial respiratory activity in astrocyte-MN interactions. These results suggest that PDK2 silencing could be a cell-specific therapeutic tool to slow the progression of ALS.
Miquel_2024_Pyruvate dehydrogenase kinase 2 knockdown astrocytes ALS.pdf
Adult aberrant astrocytes submitted to late passage cultivation lost differentiation markers and decreased their pro-inflammatory profile
Heliyon 2024 Apr 26;10(9):e30360
Gabriel Otero 1 , Carmen Bolatto 2 1 , Eugenia Isasi 1 2 , Sofía Cerri 1 , Paola Rodríguez 1 , Daniela Boragno 1 , Marta Marco 1 3 , Cristina Parada 2 , Matías Stancov 1 , María Noel Cuitinho 1 , Silvia Olivera-Bravo 1
1 Department of Neurobiology and Neuropathology (NBNP), Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. 2 Department of Histology and Embryology, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay. 3 Department of Clinical Biochemistry, School of Chemistry (UdelaR), Montevideo, Uruguay.
DOI: 10.1016/j.heliyon.2024.e30360
PMID: 38711658
Pubmed: https://pubmed.ncbi.nlm.nih.gov/38711658
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S2405-8440(24)06391-6
Abstract:
In amyotrophic lateral sclerosis (ALS), astrocytes are considered key players in some non-cell non-neuronal autonomous mechanisms that underlie motor neuron death. However, it is unknown how much of these deleterious features were permanently acquired. To assess this point, we evaluated if the most remarkable features of neurotoxic aberrant glial phenotypes (AbAs) isolated from paralytic rats of the ALS model G93A Cu/Zn superoxide dismutase 1 (SOD1) could remain upon long lasting cultivation. Real time PCR, immunolabelling and zymography analysis showed that upon many passages, AbAs preserved the cell proliferation capacity, mitochondrial function and response to different compounds that inhibit some key astrocyte functions but decreased the expression of parameters associated to cell lineage, homeostasis and inflammation. As these results are contrary to the sustained inflammatory status observed along disease progression in SOD1G93A rats, we propose that the most AbAs remarkable features related to homeostasis and neurotoxicity were not permanently acquired and might depend on the signaling coming from the injuring microenvironment present in the degenerating spinal cord of terminal rats.
Mitochondrial function and reactive oxygen species production during human sperm capacitation: Unraveling key players
FASEB J 2024 Feb 29;38(4):e23486
Pilar Irigoyen 1 2 , Santiago Mansilla 2 3 , Laura Castro 2 4 , Adriana Cassina 2 4 , Rossana Sapiro 1 2
1 Unidad Académica Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 2 Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 Departamento de Métodos Cuantitativos, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
DOI: 10.1096/fj.202301957RR
PMID: 38407497
Pubmed: https://pubmed.ncbi.nlm.nih.gov/38407497
Texto completo: https://doi.org/10.1096/fj.202301957RR
Abstract:
Sperm capacitation is a critical process for male fertility. It involves a series of biochemical and physiological changes that occur in the female reproductive tract, rendering the sperm competent for successful fertilization. The precise mechanisms and, specifically, the role of mitochondria, in sperm capacitation remain incompletely understood. Previously, we revealed that in mouse sperm mitochondrial activity (e.g., oxygen consumption, membrane potential, ATP/ADP exchange, and mitochondrial Ca2+ ) increases during capacitation. Herein, we studied mitochondrial function by high-resolution respirometry (HRR) and reactive oxygen species production in capacitated (CAP) and non-capacitated (NC) human spermatozoa. We found that in capacitated sperm from normozoospermic donors, the respiratory control ratio increased by 36%, accompanied by a double oxygen consumption rate (OCR) in the presence of antimycin A. Extracellular hydrogen peroxide (H2 O2 ) detection was three times higher in CAP than in NC sperm cells. To confirm that H2 O2 production depends on mitochondrial superoxide (
Vasotocin but not isotocin is involved in the emergence of the dominant-subordinate status in males of the weakly electric fish, Gymnotus omarorum
Horm Behav 2024 Feb:158:105446
Paula Pouso 1 , Álvaro Cabana 2 , Virginia Francia 3 , Ana Silva 4
1 Depto Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay; Unidad Bases Neurales de la Conducta, Departamento de Neurofisiología Celular y Molecular, IIBCE, Montevideo 11600, Uruguay. 2 Instituto de Fundamentos y Métodos, Facultad de Psicología, Universidad de la República, Montevideo 11800, Uruguay. 3 Depto Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay. 4 Unidad Bases Neurales de la Conducta, Departamento de Neurofisiología Celular y Molecular, IIBCE, Montevideo 11600, Uruguay; Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay. Electronic address: asilva@fcien.edu.uy.
DOI: 10.1016/j.yhbeh.2023.105446
PMID: 37945472
Pubmed: https://pubmed.ncbi.nlm.nih.gov/37945472
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0018-506X(23)00144-7
Abstract:
The establishment of the dominant-subordinate status implies a clear behavioral asymmetry between contenders that arises immediately after the resolution of the agonistic encounter and persists during the maintenance of stable dominance hierarchies. Changes in the activity of the brain social behavior network (SBN) are postulated to be responsible for the establishment and maintenance of the dominant-subordinate status. The hypothalamic nonapeptides of the vasopressin (AVP) and oxytocin (OT) families are known to modulate the activity of the SBN in a context-dependent manner across vertebrates, including status-dependent modulations. We searched for status-dependent asymmetries in AVP-like (vasotocin, AVT) and OT-like (isotocin, IT) cell number and activation immediately after the establishment of dominance in males of the weakly electric fish, Gymnotus omarorum, which displays the best understood example of non-breeding territorial aggression among teleosts. We used immunolabeling (FOS, AVT, and IT) of preoptic area (POA) neurons after dyadic agonistic encounters. This study is among the first to show in teleosts that AVT, but not IT, is involved in the establishment of the dominant-subordinate status. We also found status-dependent subregion-specific changes of AVT cell number and activation. These results confirm the involvement of AVT in the establishment of dominance and support the speculation that AVT is released from dominants' AVT neurons.
Insights into the Y chromosome human diversity in Uruguay
Am J Hum Biol 2023 35(12):e23963
Patricia Mut 1 , Bernardo Bertoni 2 , Rossana Sapiro 3 , Pedro C Hidalgo 4 , Alejandra Torres 5 , Carlos Azambuja 5 , Mónica Sans 1
1 Departamento de Antropología Biológica, Facultad de Humanidades y Ciencias de la Educación, UdelaR, Montevideo, Uruguay. 2 Departamento de Genética, Facultad de Medicina, UdelaR, Montevideo, Uruguay. 3 Departamento de Histología y Embriología, Facultad de Medicina, UdelaR, Montevideo, Uruguay. 4 Polo de Desarrollo Universitario Diversidad Genética Humana, Centro Universitario Noreste, Tacuarembó, Uruguay. 5 Genia-Genetics Molecular Laboratory, Montevideo, Uruguay.
DOI: 10.1002/ajhb.23963
PMID: 37493343
Pubmed: https://pubmed.ncbi.nlm.nih.gov/37493343
Texto completo: https://doi.org/10.1002/ajhb.23963
Abstract:
Background: With regard to the origin of its population and microevolutionary processes, Uruguay exhibits distinctive features that distinguish it from other countries in Latin America, while at the same time sharing several similarities. In this article, we will focus on the variability of paternal genetic lineages in two geographical regions with different histories that can be considered as examples of distinct populations for the continent. In general terms, the genetic diversity is a result of different demographic processes related to the American conquest and colonisation. These resulted in distinct ancestral components which vary geographical and depend on the distribution by sex within these components. In Uruguay, native maternal haplogroups are significantly more frequent in the North. Although there are several studies about the geneticvariability of Uruguay, little is known about male genetic lineages.
Aims: The aim of this work is to present an updated study of the male genetic variability of the Uruguayan population.
Methods: We analyzed 13 biallelic markers and 27 STRs located in the male-specific region of the Y chromosome for 157 males: 98 from the capital, Montevideo, and 59 from Tacuarembó.
Results: Almost all haplogroups found in both locations are European (99% and 93.2% respectively). One Sub-Saharan African haplogroup was found in Montevideo (1%) and 2 in Tacuarembó (3%), while Native haplogroups were found only in Tacuarembó, evidencing a strong sex-biased admixture. By crossing genetic and genealogical information we could relate European haplogroups with different waves and times of migrations.
Discussion: Network analysis indicated a very diverse male population, suggesting that European migrants came from heterogeneous geographic locations and in different waves. Tacuarembó has closer population affinities with Iberian populations while Montevideo is more diverse. Male population expansion expansion, can be explained by the large number of migrants that arrived during the XIX century and the first half of the XX century.
Conclusions: The Uruguayan male gene pool is the result of several migration waves with diverse origins, with strong sex-biased admixture that can be explained by the European migration, the violence against the indigenous males, and the segregation of the Africansadmixture that can be explained due to European migration, violence against Natives, and segregation against African males.admixture that can be explained due to European migration, violence against Natives, and segregation against African males.admixture that can be explained due to European migration, violence against Natives, and segregation against African males.admixture that can be explained due to European migration, violence against Natives, and segregation of hte Africans.
CD300f immune receptor contributes to healthy aging by regulating inflammaging, metabolism, and cognitive decline
Cell Rep 2023 Oct 31;42(10):113269
Frances Evans 1 , Daniela Alí-Ruiz 2 , Natalia Rego 3 , María Luciana Negro-Demontel 1 , Natalia Lago 2 , Fabio Andrés Cawen 2 , Bruno Pannunzio 1 , Paula Sanchez-Molina 4 , Laura Reyes 5 , Andrea Paolino 5 , Jorge Rodríguez-Duarte 6 , Valentina Pérez-Torrado 7 , Almudena Chicote-González 8 , Celia Quijano 9 , Inés Marmisolle 9 , Ana Paula Mulet 10 , Geraldine Schlapp 10 , María Noel Meikle 10 , Mariana Bresque 7 , Martina Crispo 10 , Eduardo Savio 5 , Cristina Malagelada 8 , Carlos Escande 7 , Hugo Peluffo 11
1 Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay. 2 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay. 3 Bioinformatics Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay; Faculty of Sciences, UDELAR, Montevideo, Uruguay. 4 Department of Cell Biology, Physiology and Immunology, and Institute of Neuroscience, Universitat Autònoma de Barcelona, Barcelona, Spain. 5 Uruguayan Center for Molecular Imaging (CUDIM), Montevideo, Uruguay. 6 Laboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay. 7 Metabolic Diseases and Aging Laboratory, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay. 8 Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Neurociències, Universitat de Barcelona (UB), Barcelona, Spain. 9 Departamento de Bioquímica y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 10 Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay. 11 Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Neurociències, Universitat de Barcelona (UB), Barcelona, Spain. Electronic address: hugo.peluffo@ub.edu.
DOI: 10.1016/j.celrep.2023.113269
PMID: 37864797
Pubmed: https://pubmed.ncbi.nlm.nih.gov/37864797
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(23)01281-0
Abstract:
Emerging evidence suggests that immune receptors may participate in many aging-related processes such as energy metabolism, inflammation, and cognitive decline. CD300f, a TREM2-like lipid-sensing immune receptor, is an exceptional receptor as it integrates activating and inhibitory cell-signaling pathways that modulate inflammation, efferocytosis, and microglial metabolic fitness. We hypothesize that CD300f can regulate systemic aging-related processes and ultimately healthy lifespan. We closely followed several cohorts of two strains of CD300f-/- and WT mice of both sexes for 30 months and observed an important reduction in lifespan and healthspan in knockout mice. This was associated with systemic inflammaging, increased cognitive decline, reduced brain glucose uptake observed by 18FDG PET scans, enrichment in microglial aging/neurodegeneration phenotypes, proteostasis alterations, senescence, increased frailty, and sex-dependent systemic metabolic changes. Moreover, the absence of CD300f altered macrophage immunometabolic phenotype. Taken together, we provide strong evidence suggesting that myeloid cell CD300f immune receptor contributes to healthy aging.
Microglial CD300f immune receptor contributes to the maintenance of neuron viability in vitro and after a penetrating brain injury
Sci Rep 2023 Oct 5;13(1):16796
Daniela Alí-Ruiz 1 2 , Nathalia Vitureira 3 , Hugo Peluffo 4 5 6 7
1 Neuroinflammation and Gene Therapy Lab., Institut Pasteur de Montevideo, Montevideo, Uruguay. 2 Departamento de Histología y Embriología, Facultad de Medicina, UdelaR, Montevideo, Uruguay. 3 Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Neuroinflammation and Gene Therapy Lab., Institut Pasteur de Montevideo, Montevideo, Uruguay. hugo.peluffo@pasteur.edu.uy. 5 Departamento de Histología y Embriología, Facultad de Medicina, UdelaR, Montevideo, Uruguay. hugo.peluffo@pasteur.edu.uy. 6 Unitat de Bioquímica i Biología Molecular, Departamento de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain. hugo.peluffo@pasteur.edu.uy. 7 Institut de Neurociències, Universitat de Barcelona (UB), Barcelona, Spain. hugo.peluffo@pasteur.edu.uy.
DOI: 10.1038/s41598-023-43840-1
PMID: 37798310
Pubmed: https://pubmed.ncbi.nlm.nih.gov/37798310
Texto completo: https://doi.org/10.1038/s41598-023-43840-1
Abstract:
Emerging evidences suggest that immune receptors participate in diverse microglial and macrophage functions by regulating their immunometabolism, inflammatory phenotype and phagocytosis. CD300f, a TREM2-like lipid sensing immune receptor, that integrates activating and inhibitory cell-signalling pathways, modulates inflammation, efferocytosis and microglial metabolic fitness. In particular, CD300f overexpression was described to be neuroprotective after an acute brain injury, suggesting a role for this immune receptor in neurotrophic interactions. Thus, we hypothesised that CD300f modulates neuronal survival through neuron-microglial interactions. In order to study its biological function, we used in vitro and in vivo approaches, CD300f-/- animals and rCD300f-Fc, a fusion protein that interrupts the endogen interaction between CD300f receptor-ligands. In hippocampal cocultures containing neurons and mixed glia, we observed that rCD300f-Fc, but not control IgGs induced neuronal death. In accordance, in vivo studies performed by injecting rCD300f-Fc or control IgGs into rat or WT or CD300 KO mice neocortex, showed an increased lesioned area after a penetrating brain injury. Interestingly, this neuronal death was dependent on glia, and the neurotoxic mechanism did not involve the increase of proinflammatory cytokines, the participation of NMDA receptors or ATP release. However, exogenous addition of glial cell line-derived neurotrophic factor (GDNF) prevented this process. Taken together, our results suggest that CD300f modulates neuronal survival in vitro and after a penetrating brain injury in vivo and that CD300f inhibition alters microglial phenotype generating a neurotoxic microenvironment.
Fertility preservation in male cancer patients. Counseling and reproductive outcomes
Front Cell Dev Biol 2023 Aug 16:11:1240152
Dana Kimelman 1 2 3 , Andrea Torrens 2 , Carla Bonelli 2 , Rossana Sapiro 4
1 Oncofertility Program, Centro Hospitalario Pereira Rossell, Administración de los Servicios de Salud del Estado (ASSE), Montevideo, Uruguay. 2 Reprovita Lab and Biobank, Montevideo, Uruguay. 3 Clínica Ginecotocológica "B", Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Unidad Académica Histologia y Embriologia, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
DOI: 10.3389/fcell.2023.1240152
PMID: 37664467
Pubmed: https://pubmed.ncbi.nlm.nih.gov/37664467
Texto completo: https://doi.org/10.3389/fcell.2023.1240152
Abstract:
Introduction: Advances in cancer treatments have determined an increase in survival rates. However, these lifesaving therapies may have a negative impact on reproductive health. To diminish the infertility risk; different fertility preservation strategies have been designed. Sperm freezing is the gold standard fertility preservation method in the case of post-pubertal men. The main objective of this study is to evaluate the fertility status of Uruguayan male cancer survivors who have gone through sperm freezing, as well as to assess oncofertility counseling received by these patients. Methods: This is a descriptive, cross-sectional, observational, and transversal study. A survey was conducted on male cancer survivors who cryopreserved sperm between 1985 and 2021 in "Reprovita Lab and Biobank" which is the only sperm bank in this country. Results: One hundred thirty-five participants answered the survey. At the time of diagnosis, the mean age of patients was 28.8 ± 6.4 years old. Testicular was the most frequent type of cancer (64%). Only, 12% (n = 15) already had children at the time of diagnosis. Among the interviewed survivors, 50% (n = 62) attempted to conceive after cancer treatment, and 68% (n = 42) achieved natural pregnancy. Patients who did not achieve spontaneous conception (n = 11), used their cryopreserved samples, and 45.4% achieved pregnancy. About 86% (n = 107) of survivors believed that the timing of oncofertility referrals was appropriate and 97% considered that having the possibility of protecting their fertility was very important. Eighty percent (n = 101), were advised by their attending physicians, 14% (n = 18) sought advice from family members or friends, and 4% (n = 5) from oncofertility specialists. Discussion: To our knowledge, this is the first study evaluating the reproductive outcomes of male cancer survivors in our country and the region. Most of the interviewed survivors considered fertility preservation as a positive initiative, independent of their reproductive outcomes, reflecting the importance of fertility preservation counseling as one of the most important aspects for futurequality of life of young cancer patients.
Rod precursors in the adult retina of the Austrolebias charrua annual fish
Tissue Cell 2023 83:102150
M L Herrera 1 , S Silva 2 , I Berrosteguieta 2 , G Casanova 3 , J C Rosillo 4 , A S Fernández 5
1 Departamento Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay; Sección Fisiología y Nutrición, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. 2 Departamento Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay. 3 Unidad de Microscopía Electrónica, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. 4 Departamento Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Avda. General Flores 2125, 11800 Montevideo, Uruguay. Electronic address: jrosillo@iibce.edu.uy. 5 Departamento Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay; Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. Electronic address: afernandez@iibce.edu.uy.
DOI: 10.1016/j.tice.2023.102150
PMID: 37423033
Pubmed: https://pubmed.ncbi.nlm.nih.gov/37423033
Texto completo: https://www.sciencedirect.com/science/article/abs/pii/S0040816623001386?via%3Dihub
Abstract:
Rod photoreceptors in the adult teleost retina are produced by rod precursors located in the outer nuclear layer (ONL). Annual fishes of the genus Austrolebias exhibit extensive adult retinal cell proliferation and neurogenesis, as well as surprising adaptive strategies to their extreme and changing environment, including adult retinal plasticity. Thus, here we identify and characterize rod precursors in the ONL of the Austrolebias charrua retina. For this aim we used classical histological techniques, transmission electron microscopy, detection of cell proliferation, and immunohistochemistry. Through these complementary approaches, we describe a cell population clearly distinguishable from photoreceptors in the ONL of the adult retina of A. charrua, which we propose corresponds to the rod precursor population. These cells exhibited particular morphological and ultrastructural characteristics, uptake of cell proliferation markers (BrdU+) and expression of stem cell markers (Sox2+). Determining the existence of the population of rod precursors is crucial to understand the sequence of events related to retinal plasticity and regeneration.
Morphological evidence of the protective effects of a synthetic chalcone against the striatal myelin damage induced by glutaric acid
Int J Dev Neurosci 2023 83(3):274-296
Gabriela Casanova 1 2 3 , Juan Carlos Rosillo 2 4 , Marcie Jiménez 1 , Anabel Fernández 2 5 , Magela Rodao 1 , Gaby Martínez 1 , Eugenia Isasi 3 4 , Nadia Presa Gau 6 , Gabriel Otero 3 6 , Mauricio Cabrera 6 , Pablo Díaz-Amarilla 3 , Hugo Cerecetto 6 , Mercedes González 6 , Silvia Olivera-Bravo 3
1 Unidad de Microscopía Electrónica, Facultad de Ciencias, Universidad de la República (UdelaR), Montevideo, Uruguay. 2 Laboratorio de Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Ministerio de Educación y Cultura (MEC), Montevideo, Uruguay. 3 Laboratorio de Neurobiología Celular y Molecular, IIBCE, MEC, Montevideo, Uruguay. 4 Departamento de Histología y Embriología, Facultad de Medicina, UdelaR, Montevideo, Uruguay. 5 Laboratorio de Neurociencias, Facultad de Ciencias, UdelaR, Montevideo, Uruguay. 6 Grupo de Química Orgánica Medicinal, Facultad de Ciencias, UdelaR, Montevideo, Uruguay.
DOI: 10.1002/jdn.10256
PMID: 37073624
Pubmed: https://pubmed.ncbi.nlm.nih.gov/37073624
Texto completo: https://doi.org/10.1002/jdn.10256
Abstract:
Ultrastructural features of striatal white matter and cells in an in vivo model of glutaric acidemia type I created by intracerebral injection of glutaric acid (GA) were analyzed by transmission electron microscopy and immunohistochemistry. To test if the white matter damage observed in this model could be prevented, we administered the synthetic chemopreventive molecule CH38 ((E)-3-(4-methylthiophenyl)-1-phenyl-2-propen-1-one) to newborn rats, previous to an intracerebroventricular injection of GA. The study was done when striatal myelination was incipient and when it was already established (at 12 and 45 days post-injection [DPI], respectively). Results obtained indicate that that the ultrastructure of astrocytes and neurons did not appear significantly affected by the GA bolus. Instead, in oligodendrocytes, the most prominent GA-dependent injury defects included endoplasmic reticulum (ER) stress and nuclear envelope swelling at 12 DPI. Altered and reduced immunoreactivities against heavy neurofilament (NF), proteolipid protein (PLP), and myelin-associated glycoprotein (MAG) together with axonal bundle fragmentation and decreased myelin were also found at both ages analyzed. CH38 by itself did not affect striatal cells or axonal packages. However, the group of rats that received CH38 before GA did not show evidence neither of ER stress nor nuclear envelope dilation in oligodendrocytes, and axonal bundles appeared less fragmented. In this group, labeling of NF and PLP was similar to the controls. These results suggest that the CH38 molecule is a candidate drug to prevent or decrease the neural damage elicited by a pathological increase of GA in the brain. Optimization of the treatments and identification of the mechanisms underlying CH38 protective effects will open new therapeutic windows to protect myelin, which is a vulnerable target of numerous nervous system diseases.