Publicaciones por año
Publicaciones del Departamento de Histología y Embriología
CD200R1 modulates myelin phagocytosis and spleen response following spinal cord injury
Sci Re 2026 15(1):41013
Bruno Pannunzio 1 2 , Fabio Andrés Cawen 1 3 4 , Frances Evans 1 2 , Rubèn López-Vales 5 6 , Hugo Peluffo 1 3 4 , Natalia Lago 7 8 9
1 Institut Pasteur de Montevideo, Montevideo, Uruguay. 2 Histology and Embryology Department, Faculty of Medicine, Universidad de la República, Montevideo, Uruguay. 3 Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, 08036, Spain. 4 Institut de Neurociències, Universitat de Barcelona (UB), Barcelona, 08036, Spain. 5 Departament de Biologia Cel·lular, Fisiologia i Immunologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain. 6 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. 7 Institut Pasteur de Montevideo, Montevideo, Uruguay. Natalia.Lago@uab.cat. 8 Departament de Biologia Cel·lular, Fisiologia i Immunologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain. Natalia.Lago@uab.cat. 9 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Natalia.Lago@uab.cat.
DOI: 10.1038/s41598-025-24827-6
PMID: 41266433
Pubmed: https://pubmed.ncbi.nlm.nih.gov/41266433
Texto completo: https://doi.org/10.1038/s41598-025-24827-6
Abstract:
The interaction between CD200 and its receptor CD200R1 plays a key role in modulating immune responses in nervous system disorders. This study explored the function of CD200R1 in local and systemic inflammation following spinal cord injury (SCI) using CD200R1-knockout (CD200R1-/-) mice. Following a low thoracic contusion injury, CD200R1-/- mice exhibited increased macrophage infiltration at the injury site, with a greater proportion of pro-inflammatory Ly6C + macrophages. Myelin phagocytosis was impaired in CD200R1-/- macrophages both ex vivo and in vitro, indicating a reduced capacity to clear myelin debris. Despite these immune alterations, CD200R1 deficiency did not affect spontaneous locomotor recovery post-SCI, as measured by the Basso Mouse Scale. However, CD200R1-/- mice tended to lose more weight after injury, suggesting systemic effects. In uninjured (naïve) conditions, CD200R1-/- mice showed reduced spleen weight and lymphocyte counts, along with lower mRNA expression of inflammatory cytokines TNFα, IL6, and CCL2, though no significant differences were seen in splenic immune cell populations. Altogether, these results suggest that CD200R1 is an important factor regulating myelin phagocytosis by macrophages and maintaining normal immune and splenic homeostasis under both injured and naïve conditions.
Editorial: Biomarker discovery and validation in neurological diseases
Front Cell Neurosci 2026 20:1877174
Shivani Singla 1 , Bhupesh Vaidya 1 , Laura Martínez-Palma 2 3 , Dirk M Hermann 4
1 Texas Medical Center, Houston, TX, United States. 2 Academic Unit Histology & Embryology, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 ALS Center of Uruguay (CELAU), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
DOI: 10.3389/fncel.2026.1877174
PMID: 42282855
Pubmed: https://pubmed.ncbi.nlm.nih.gov/42282855
Texto completo: https://doi.org/10.3389/fncel.2026.1877174
Abstract:
Editorial: Biomarker discovery and validation in neurological diseases
Front Cell Neurosci 2026 20:1877174
Shivani Singla 1 , Bhupesh Vaidya 1 , Laura Martínez-Palma 2 3 , Dirk M Hermann 4
1 Texas Medical Center, Houston, TX, United States. 2 Academic Unit Histology & Embryology, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 ALS Center of Uruguay (CELAU), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
DOI: 10.3389/fncel.2026.1877174
PMID: 42282855
Pubmed: https://pubmed.ncbi.nlm.nih.gov/42282855
Texto completo: https://doi.org/10.3389/fncel.2026.1877174
Abstract:
Monoclonal antibodies against nitrated nerve growth factor reveal an oxidation-dependent pathogenic hallmark in ALS
Proc Natl Acad Sci U S A 2026 28;123(17):e2536562123
Valentina Varela # 1 , Santiago Garcimartín # 2 3 , Emiliano Trias # 4 , Ari Zeida 2 3 5 , Monique Richter 1 , Andrés de León 1 , Ernesto Miquel 6 , Peter H King 7 8 , Brigitte Vulliez-Le Normand 9 , Mariano Martinez 9 , Pedro M Alzari 9 , Silvina Bartesaghi 2 3 5 , Rafael Radi 2 3 5 , Luis Barbeito 1
1 Laboratorio de Neurodegeneración, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay. 2 Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay. 3 Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la Republica, Montevideo 11800, Uruguay. 4 Departamento de Neurobiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable Montevideo, Montevideo 11600, Uruguay. 5 Programa de Alimentos y Salud Humana (PAyS), Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay. 6 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay. 7 Department of Neurology and Killion Center for Neurodegeneration and Experimental Therapeutics, University of Alabama, Birmingham, AL 35294. 8 Birmingham Veterans Affairs Health Care System, Birmingham, AL 35295. 9 Unité de Microbiologie Structurale, Département de Biologie Structurale et Chimie, Institut Pasteur, CNRS, Université Paris Cité, Paris 75015, France. # Contributed equally.
DOI: 10.1073/pnas.2536562123
PMID: 42030149
Pubmed: https://pubmed.ncbi.nlm.nih.gov/42030149
Texto completo: https://doi.org/10.1073/pnas.2536562123
Abstract:
Nerve growth factor (NGF) is a member of the neurotrophin family, essential for neuronal survival and phenotypic maintenance. However, in vitro, its function can be disrupted by oxidative posttranslational modifications such as tyrosine nitration. Nitrated NGF (NO2NGF) has been shown to have a gain-of-toxic, pro-apoptotic, activity in motoneuron cultures. Herein, we report the generation and characterization of monoclonal antibodies (mAbs) that specifically recognize NO2NGF to unravel its formation in vivo. Using hybridoma technology, we produced mAbs with high affinity and selectivity for NO2NGF, as demonstrated immunochemically and by surface plasmon resonance. The antibodies elicit neutralizing capacity to NO2NGF in neuronal cells. Nitrated Tyr52 within the NGF48-58 sequence was identified as the primary antigenic determinant by crystallographic analysis of antibody:peptide complexes at atomic resolution, peptide-based epitope mapping and molecular dynamics simulations, whereas local sequence NGF motifs around the nitrated tyrosine are important for protein specificity. The antibodies revealed NO2NGF accumulation in amyotrophic lateral sclerosis (ALS) rodent models and human subjects. Indeed, immunofluorescence showed selective accumulation of NO2NGF in spinal cord regions undergoing motor neuron degeneration, as well as in sciatic nerves and neuromuscular junctions. Our findings establish NGF nitration as an oxidative hallmark in ALS and demonstrate that monoclonal antibodies targeting this chemical modification are powerful tools for both mechanistic studies and biomarkers development. This work proposes a link between neurotrophin nitration and neurodegenerative disease progression and opens avenues for therapeutic exploration along the peroxynitrite-tyrosine nitration pathway.
Modulation of cofilin 1 phosphorylation induces juvenile-like plasticity in the adult mouse visual cortex
Neuroscience 2026 595:262-269
Agustina Dapueto 1 , Emilia Hayek 2 , Alejo Acuña 3 , Bruno Pannunzio 4 , Leonel Gomez 5 , Francesco M Rossi 6
1 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay; Present address: Laboratorio de Mecanismos de Neurodegeneración y Neuroprotección, Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. Electronic address: agustinadapueto@gmail.com. 2 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address: hayekemilia03@gmail.com. 3 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address: alejoacu@gmail.com. 4 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay; Present address: Departamento de Histología y Embriología, Facultad de Medicina, UdelaR / Laboratorio de Neuroinflamación y Terapia Génica del Institut Pasteur de Montevideo, Uruguay. Electronic address: brunopannunzio@gmail.com. 5 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address: leonel.gomez@gmail.com. 6 Laboratorio de Neurociencias "Unidad de Neuroplasticidad", Instituto de Biología, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address: fmrossi@fcien.edu.uy.
DOI: 10.1016/j.neuroscience.2026.01.003
PMID: 41506312
Pubmed: https://pubmed.ncbi.nlm.nih.gov/41506312
Texto completo: https://www.sciencedirect.com/science/article/pii/S0306452226000035
Abstract:
Cofilin 1 is an actin-depolymerizing protein that plays a fundamental role in actin dynamics, particularly within dendritic spines, where it has been implicated in both structural and functional plasticity. We recently demonstrated, using a combination of differential proteomics, western blot and immunohistochemistry, that the expression of cofilin 1 and its inactive phosphorylated form is dynamically regulated in the mouse visual cortex. Expression levels change across critical periods of postnatal development and are modulated by visual experience, suggesting that cofilin 1 plays a dynamic role in synaptic remodeling during windows of heightened cortical plasticity. In this study, we sought to determine whether cofilin 1 influences experience-dependent plasticity in the adult visual cortex, a stage where plasticity is more restricted but still inducible under specific conditions. Specifically, we administered a synthetic peptide inhibitor of cofilin 1 activity in vivo (PCOF). Following monocular deprivation, adult mice received either the PCOF peptide or a control peptide. Structural plasticity was assessed by quantifying dendritic spine density using Golgi-like staining, while visual plasticity was evaluated by measuring visual acuity through the optomotor response test. Our results show that, in adult mice treated with the PCOF peptide - but not in controls - monocular deprivation led to a significant reduction in dendritic spine density in the contralateral visual cortex, as well as a decrease in visual acuity of the previously deprived eye. These findings indicate that cofilin 1 activity is crucial for the regulation of experience-dependent plasticity in the adult mouse visual cortex.
Tembleque (SDtq) rat: A new model of leukodystrophy associated with hypomyelination and impaired oligodendrocyte maturation
Lab Anim. 2026 60(1):63-74
Martín Breijo 1 , Florencia Fontes 1 , Mariela Santos 1 , Laura Martínez Palma 2 , Sergio Rocha 1 , Patricia Genovesse 3 , Bin Liu 4 , David Aghado 4 , Carlos Perez 4 , Fernando Benavides 4
1 Unidad de Reactivos y Biomodelos de Experimentación, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 Departamento de Histología y Embriología, Facultad de Veterinaria, Montevideo, Uruguay. 4 Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, USA.
DOI: 10.1177/00236772251369173
PMID: 41914324
Pubmed: https://pubmed.ncbi.nlm.nih.gov/41914324
Texto completo: https://doi.org/10.1177/00236772251369173
Abstract:
This work presents the characterization of tembleque (SDtq) rats as a novel animal model for myelination abnormalities, primarily manifesting as tremors and ataxia, which notably declined by 16 weeks of age. This model originated from a spontaneous autosomal recessive mutation in an outbred Sprague Dawley colony. Histological and electron microscopy analyses revealed significant hypomyelination in the central nervous system of SDtq rats compared with wild-type controls. The thoracic spinal cords of SDtq rats exhibited reduced white matter areas, while the gray matter remained consistent. Peripheral nerves showed no change in myelin thickness, though a decrease in axonal diameter was observed. Transcript analysis indicated reduced expression of mature oligodendrocyte markers and increased activity of astrocytes and microglia in SDtq rats, suggesting compensatory mechanisms. Preliminary mapping studies showed that the causative mutation is located on proximal chromosome 19. These findings highlight the SDtq rat as a promising model for studying the underlying biology of myelin disorders and the role of glial cells in leukodystrophies.
Neuroscience in Latin America Five Decades of Flourishing Neurochemistry in the Region
J Neurochem 2026 170(2):e70349
J M Pasquini 1 , F C A Gomes 2 , R A de Melo Reis 2 , P Cassina 3 , L Barbeito 4 , S Olivera 5
1 Depto Química Biológica e IQUIFIB Facultad Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. 2 Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 3 Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Institut Pasteur, Montevideo, Uruguay. 5 Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
DOI: 10.1111/jnc.70349
PMID: 41607077
Pubmed: https://pubmed.ncbi.nlm.nih.gov/41607077
Texto completo: https://doi.org/10.1111/jnc.70349
Abstract:
We describe the development of neurochemistry in Brazil, Argentina, Uruguay, and Chile in the XX century through Latin American scientists who pioneered the discipline in their countries. In addition, we analyze the research groups that succeeded the pioneers and the fields explored in greater depth in different countries. We examine the history of glial cell research and the efforts made despite financial constraints. We also highlight the role of the International Society of Neurochemistry (ISN) in the history of neurochemistry in Latin America. A special section is dedicated to neurochemistry in Venezuela, given its significant role in the past.
Environmental drivers of calling activity in a southern subtropical anuran assemblage: insights from passive acoustic monitoring
Bioacoustics 2026 35(1), 75–89
Pouso, P 1, Cabana, Á 2, Nieto Methol, C 1
1 Laboratorio Bases Neurales de la Comunicación Acústica, Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 2 CICADA and Instituto de Fundamentos y Métodos, Facultad de Psicología, Universidad de la República, Montevideo, Uruguay
DOI: 10.1080/09524622.2025.2597859
PMID:
Pubmed: https://pubmed.ncbi.nlm.nih.gov/
Texto completo: https://www.tandfonline.com/doi/full/10.1080/09524622.2025.2597859
Abstract:
In anurans, acoustic communication is a crucial reproductive behaviour shaped by individual traits, social interactions and environmental cues. External factors such as temperature, rainfall and photoperiod can elicit physiological responses that drive behavioural rhythms at individual and population scales. While temperature and rainfall effects on anuran calling activity are well-established, photoperiodic influences remain comparatively understudied, particularly within southern subtropical assemblages. We assessed hourly calling activity of Boana pulchella in Uruguay over a 12-month period using Passive Acoustic Monitoring (PAM) and validated semi-automated data processing methods to examine environmental drivers in a subtropical permanent pond. Calling behaviour increased during the warmer months, showing a clear seasonal pattern. Peak activity timing remained consistent across seasons, but the temporal window of vocalisations expanded during winter (long nights) and contracted during summer (long days), reflecting photoperiodic variation. Linear regression analyses showed significant effects of photoperiod, temperature and their interaction on calling activity, while rainfall and atmospheric pressure showed no effect. These findings underscore the regulatory role of photoperiod in shaping reproductive acoustic behaviour and highlight the need to further explore its physiological and adaptive significance, especially within underrepresented subtropical assemblages.
Fluorescence Lifetime Microscopy Methods for Studying Dynamics of Fluorescent Proteins In Vivo and In Vitro
Adv Exp Med Biol 2026 1496:335-362
Bruno Pannunzio 1 2 , Leonel Malacrida 3 4
1 Advanced Bioimaging Unit, Institut Pasteur de Montevideo and Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay. 2 Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 Advanced Bioimaging Unit, Institut Pasteur de Montevideo and Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay. lmalacrida@pasteur.edu.uy. 4 Unidad Académica de Fisiopatología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. lmalacrida@pasteur.edu.uy.
DOI: 10.1007/978-3-032-07511-6_13
PMID: 41652170
Pubmed: https://pubmed.ncbi.nlm.nih.gov/41652170
Texto completo: https://dx.doi.org/10.1007/978-3-032-07511-6_13
Abstract:
Fluorescence-based microscopy techniques are key tools for studying protein dynamics in vivo, enabling real-time tracking of molecular interactions with high specificity and subcellular resolution. Fluorescence lifetime imaging microscopy (FLIM) provides quantitative insights into the microenvironment of fluorophores by measuring their excited-state decay times, independent of intensity-based variations such as concentration and photobleaching. The phasor approach to FLIM simplifies lifetime analysis by mapping decay dynamics onto a two-dimensional plot, eliminating complex fitting procedures and allowing real-time visualization of heterogeneous fluorescence signals. This approach enhances the detection of subtle microenvironmental changes, facilitating the study of protein interactions. This chapter explores the application of FLIM in molecular interaction studies, with a focus on Förster resonance energy transfer (FRET). Combining FLIM with FRET (FRET-FLIM) enables precise quantification of energy transfer efficiency, overcoming the limitations of intensity-based FRET measurements. Additionally, integrating FLIM with stimulated emission depletion (FLIM-STED) super-resolution microscopy extends the spatial resolution beyond the diffraction limit, allowing for the nanoscale mapping of protein distributions and interactions. Together, these advanced techniques provide powerful tools for investigating dynamic cellular processes with high temporal and spatial resolution, offering new perspectives on protein function and biomolecular mechanisms in living systems.
CD300f enables microglial damage sensing, efferocytosis, and apoptotic cell metabolization after brain injury
Brain Behav Immun 2025 130:106105
Luciana Negro-Demontel 1 , Frances Evans 2 , Fabio Andrés Cawen 3 , Zachary Fitzpatrick 4 , Hannah D Mason 4 , Daniela Alí-Ruiz 5 , Rubèn López-Vales 6 , Natalia Lago 6 , Hugo Peluffo 7
1 Department of Histology and Embriology, School of Medicine, UDELAR, Montevideo, 11800, Uruguay; Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay; National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, USA. Electronic address: Lucianan@wustl.edu. 2 Department of Histology and Embriology, School of Medicine, UDELAR, Montevideo, 11800, Uruguay; Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay. 3 Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay; Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), 08036, Spain; Institut de Neurociències, Universitat de Barcelona (UB), 08036, Spain. 4 National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, USA. 5 Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay. 6 Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona (UAB), Spain; Institut de Neurociències, Autonomous University of Barcelona (UAB), Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. 7 Institut Pasteur de Montevideo, Montevideo, 11400, Uruguay; Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), 08036, Spain; Institut de Neurociències, Universitat de Barcelona (UB), 08036, Spain. Electronic address: hugo.peluffo@ub.edu.
DOI: 10.1016/j.bbi.2025.106105
PMID: 40935207
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40935207
Texto completo: https://www.sciencedirect.com/science/article/pii/S0889159125003472?via%3Dihub
Abstract:
Microglia, the resident phagocytes of the central nervous system (CNS), continuously survey the parenchyma and its borders, acting as first responders to brain injury. Their ability to detect and react to environmental changes is mediated by a repertoire of surface receptors collectively known as themicroglial sensome. Here, we identify the lipid-sensing immunoreceptor CD300f as a key regulator of microglial responses to tissue damage and apoptotic cells. Using intravital two-photon microscopy, we show that CD300f-/- microglia fail to extend processes toward a laser-induced cortical lesion, indicating impaired detection of damage-associated cues. In models of mild traumatic brain injury (mTBI) and intracortical injection of apoptotic cells, CD300f deficiency led to reduced recognition and clearance of dying cells resulting in the accumulation of cellular debris within the parenchyma. At later stages, apoptotic remnants were retained within CD300f-/- microglia in vivo and bone marrow-derived macrophages in vitro, suggesting defective intracellular degradation. Proteomic analysis after a controlled cortical injury (CCI) contusion model revealed widespread dysregulation of autophagy-related and metabolic pathways, consistent with impaired efferocytosis and phagolysosomal processing. In parallel, we observed upregulation of the UDP-degrading ectonucleotidase ENTPD6 protein and downregulation of the microglial purinergic receptor P2ry6 mRNA, indicating a dysfunctional UDP-P2RY6 axis that may underlie impaired damage sensing and phagocytic initiation. Despite greater histological preservation, CD300f-/- mice exhibited worse long-term functional recovery after brain injury. Together, these findings highlight CD300f as a key damage-associated molecular pattern (DAMP) receptor that integrates purinergic signaling, efferocytosis, and metabolic adaptation, highlighting its essential role in coordinating microglial responses to CNS injury.