Publicaciones por año
Publicaciones del Departamento de Histología y Embriología
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.
Morphometric analysis of the sperm midpiece during capacitation
Tissue Cell 2025 Aug:95:102866
M F Skowronek 1 , S Pietroroia 1 , D Silvera 2 , M Ford 1 , A Cassina 3 , F Lecumberry 2 , R Sapiro 4
1 Unidad Académica Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 2 Departamento de Procesamiento de Señales, Facultad de Ingeniería, Universidad de la República, Montevideo, Uruguay. 3 Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4 Unidad Académica Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Electronic address: rossanasapiro@gmail.com.
DOI: 10.1016/j.tice.2025.102866
PMID: 40157222
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40157222
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0040-8166(25)00146-6
Abstract:
In mammalian sperm, mitochondria are very densely packed and form a helical sheath in the midpiece of the flagellum. Mitochondria from somatic cells can rapidly change shape to adapt to environmental conditions. During capacitation, mammalian spermatozoa undergo morphological and physiological changes to acquire fertilization ability, evidenced by changes in sperm motility patterns (hyperactivation) and the ability to perform the acrosome reaction. Whether there are changes in sperm mitochondrial morphology during capacitation is unknown. This work aimed to quantify morphometric changes in the sperm midpiece during capacitation. Using mitochondrial fluorescent probes and a combination of freely available software, we quantified the dimensions and fluorescence intensity of the midpiece. After capacitation, the area occupied by the mitochondria decreased due to a reduction in the width but not the length of the midpiece. The decrease in the area of the midpiece occurred in spermatozoa that underwent the acrosome reaction, suggesting a reorganization of the mitochondria during capacitation. Ultrastructural analysis supported these results. The application of image processing to fluorescence microscopy images may help to identify morphological changes during capacitation.
Pericyte pannexin1 controls cerebral capillary diameter and supports memory function
Nat Commun 2025 16(1):6128
Sandra Mai-Morente 1, Eugenia Isasi 2, Alberto Rafael 1, Gonzalo Budelli 3, Silvia Olivera-Bravo 4, Nathalia Vitureira 1, Verónica Abudara 1
1 Departamento de Fisiología, 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 Biofísica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 4 Departamento de Neurobiología y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay
DOI: 10.1038/s41467-025-61312-0
PMID: 40610448
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40610448
Texto completo: https://www.nature.com/articles/s41467-025-61312-0
Abstract:
In the blood-brain-barrier, contractile pericytes fine-tune the capillary resistance and blood supply to meet neuro-metabolic demands; molecular players governing these functions remain unclear. Here we show that mice cerebral pericytes express functional pannexin1 (Panx1) channels, which drive efflux of ATP, a key activator of pericyte contractility. In hippocampal slices, pericyte Panx1 mediates capillary diameter changes in response to extracellular ATP fluctuations and glutamatergic synaptic transmission, known to contribute functional hyperaemia. Pharmacological inhibition of Panx1 in mice induces capillary widening in the cortex and hippocampus. Genetic deletion of pericyte Panx1 disrupts learning-evoked capillary dilation and memory performance. Mechanistically, glutamatergic NMDA/AMPA and purinergic P2X7/P2Y6 receptors modulate pericyte Panx1 activity, which ultimately adjusts ATP release, pericyte Ca2+ signalling and capillary dynamics. Our study unveils pericyte Panx1 as a physiological regulator of cerebral capillary diameter, which sustains brain function and serves as a potential therapeutic target for cerebrovascular cognitive disorders.
Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpiece
Front. Cell Dev. Biol. 2025 13:1609081
María Fernanda Skowronek 1 , Santiago Pietroroia 1 , Gabriel de Cola 2 , Mauricio Ramos 2 , Diego Silvera 2 , Gabriela Casanova 3 , Federico Lecumberry 2 , Adriana Cassina 4 5 , Rossana Sapiro 1 5
1 Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 2 Departamento de Procesamiento de Señales, Facultad de Ingeniería, Universidad de la República, Montevideo, Uruguay 3 Unidad de Microscopía Electrónica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay 4 Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 5 Centro de Investigaciones Biomédicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
DOI: 10.3389/fcell.2025.1609081
PMID: 40556737
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40556737
Texto completo: https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1609081/full
Abstract:
Introduction: The male factor is responsible for 50% of infertility cases. Numerous studies have explored the relationship between human sperm morphology assessed via optical and electron microscopy and reproductive outcomes. In the sperm midpiece, mitochondria are arranged in a helical shape, forming a compact sheath. Disruptions in this precise mitochondrial structure, size, or organization may contribute to infertility. However, despite established links between abnormal sperm morphology and pathology, mitochondrial abnormalities in sperm remain relatively understudied.
Methods: In this study, we employed computational image analysis and fluorescence labelling to quantitatively assess morphometric changes in the sperm midpiece and correlate these findings with mitochondrial ultrastructure in fertile and infertile men.
Results: Our results revealed a significant increase in midpiece area, width, and roundness in sperm from men with teratozoospermia. These findings were further validated by electron microscopy. The ultrastructural morphometric analysis demonstrated disassembled, enlarged, and irregularly shaped mitochondria in sperm from infertile men. Additionally, we applied ultrastructural morphometric analyses to apoptotic sperm samples, observing similar qualitative and quantitative mitochondrial alterations, particularly in those from infertile individuals.
Discussion: Traditional sperm morphology assessments are inherently subjective, but this limitation can be addressed through quantitative morphometric analysis. Enhancing the objectivity and precision of such evaluations is essential for elucidating the biological mechanisms of male infertility and optimizing assisted reproductive technologies. In our study, spermatozoa with poor morphology (<4%) and proximal flagellar abnormalities displayed significantly shorter and wider midpieces. Ultrastructural analysis further revealed that mitochondria in sperm from infertile men were significantly larger and more irregular in shape compared to those from fertile men. These findings indicate an association between altered midpiece morphometry, mitochondrial ultrastructure, and male infertility. The integration of computational tools for automated detection and quantification of these morphological changes offers a promising avenue to improve diagnostic accuracy and deepen our understanding of male reproductive disorders.
Prenatal valproate exposure alters barrel cortex morphology in rats
Neurosci Lett 2025 138277
Diego Méndez 1 , Natalia Uriarte 2 , Marcela Espino 3 , Mauricio Ramos 4 , Federico Lecumberry 5 , Javier Nogueira 6
1 Unidad Académica Anatomía Patológica, Facultad de Medicina, Universidad de la República, Uruguay; Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Uruguay. Electronic address: diegomendez@fmed.edu.uy. 2 Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Uruguay. Electronic address: natiuria@fcien.edu.uy. 3 Unidad Académica Anatomía Patológica, Facultad de Medicina, Universidad de la República, Uruguay; Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Uruguay. 4 Instituto de Ingeniería Eléctrica, Facultad de Ingeniería, Universidad de la República, Uruguay. Electronic address: mramos@fing.edu.uy. 5 Instituto de Ingeniería Eléctrica, Facultad de Ingeniería, Universidad de la República, Uruguay. Electronic address: lecumberry@fing.edu.uy. 6 Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Uruguay. Electronic address: nogueira@fmed.edu.uy.
DOI: 10.1016/j.neulet.2025.138277
PMID: 40447252
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40447252
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(25)00165-X
Abstract:
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition influenced by genetic and environmental factors. Prenatal exposure to valproic acid (VPA) has been linked to morphological and behavioral abnormalities resembling ASD symptoms in humans. The whisker somatosensory system in rodents serves as an optimal model for studying ASD-related sensory alterations due to its well-defined modular and somatotopic organization. In this study, we analyzed whisker cortical maps in VPA-exposed rats using cytochrome oxidase histochemistry. Our results revealed significant alterations in the primary somatosensory cortex, including a reduction in total whisker map area and poorly defined cortical barrels. Additionally, some adjacent barrels exhibited fusion, and barrel row curvature was significantly reduced, suggesting disrupted somatotopic organization. These findings align with previous studies in genetic ASD models, such as Mecp2-knockout mice, which show reduced thalamocortical connectivity and structural changes in layer IV neurons. Moreover, recent research suggests that sensory deficits in ASD may also involve dysfunctions in the peripheral nervous system. Our study highlights the relevance of somatosensory cortical map alterations in environmentally induced ASD models. Further investigations into both central and peripheral nervous system contributions could provide valuable insights into the sensory deficits underlying ASD.
Primordial Follicle Response to Two Methods of Ovarian Cortex Retrieval and Vitrification: A Pilot Study
Cureus 2025 17(5): e84918
Rebeca Chávez-Genaro 1 , Gabriel Anesetti 1 , Lorena Bonjour 1 , Clara Fernández 1 , Agustina Toledo 1 , Karina Hernández 1 , Natalibeth Barrera 2 , Lidia Cantú 2 , Dana Kimelman 3
1. Histology and Embryology, Universidad de la República, Montevideo, URY 2. Embryology, Centro de Esterilidad Montevideo, Montevideo, URY 3. Gynecology, Centro Hospitalario Pereira Rossell, Administración de los Servicios de Salud del Estado, Montevideo, URY
DOI: 10.7759/cureus.84918
PMID: 40575194
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40575194
Texto completo: https://www.cureus.com/articles/367394#!/
Abstract:
Cryopreservation and transplantation of ovarian cortical tissue are novel techniques to preserve fertility in young patients undergoing gonadotoxic treatments that may affect fertility. Vitrification has demonstrated growing success in restoring ovarian function and achieving pregnancy post-grafting. It helps maintain communication between follicles and interstitial tissue, which is essential for follicular growth. This study compares two ovarian cortex dissection techniques (strips and layers) using an ovine animal model. The results indicate that manipulation of the ovarian cortex affects primordial follicle activation and stromal tissue during vitrification, potentially compromising oocyte viability and reproductive potential. Additionally, the distribution of primordial follicles in ovarian tissue varies, influencing transplantation efficiency. Both dissection methods increase follicle activation, suggesting that mechanical manipulation impacts outcomes. These findings underscore the need to optimize tissue processing to enhance fertility preservation, particularly by understanding the roles of the stromal and extracellular matrix (ECM) in maintaining follicle dormancy and viability post-vitrification and reimplantation.
Adult neurogenesis in the Uruguayan teleost species Austrolebias charrua and Gymnotus omarorum
Neuroscience 2025 May 7:573:143-153
María E Castelló 1 , Valentina Olivera-Pasilio 2 , Juan Carlos Rosillo 3 , Anabel S Fernández 4
1 Laboratorio de Desarrollo Y Evolución Neural, Departamento de Neurociencias Integrativas Y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable, (IIBCE-MEC), Avenida. Italia 3318 11600 Montevideo, Uruguay. Electronic address: mcastello@iibce.edu.uy. 2 Laboratorio de Desarrollo Y Evolución Neural, Departamento de Neurociencias Integrativas Y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable, (IIBCE-MEC), Avenida. Italia 3318 11600 Montevideo, Uruguay; Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: valentina.oliverapasilio@northwestern.edu. 3 Laboratorio de Neurobiología Comparada, Departamento Neurociencias Integrativas Y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE-MEC), Uruguay; Departamento de Histología Y Embriología, Facultad de Medicina, UdelaR. Avda. General Flores 2125 11800 Montevideo, Uruguay; Departamento de Neurobiología Y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE-MEC), Avenida. Italia 3318 11600 Montevideo, Uruguay. Electronic address: jrosillo@iibce.edu.uy. 4 Laboratorio de Neurobiología Comparada, Departamento Neurociencias Integrativas Y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE-MEC), Uruguay; Laboratorio de Neurociencias, Instituto de Biología, Facultad de Ciencias, UdelaR, Iguá 4225 11400 Montevideo, Uruguay. Electronic address: afernandez@iibce.edu.uy.
DOI: 10.1016/j.neuroscience.2025.03.027
PMID: 40101892
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40101892
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(25)00229-5
Abstract:
Neurogenesis -the process by which new neurons are generated in the brain- is critical for nervous system development and plasticity. Adult neurogenesis underlies growth, repair, and adaptation to environmental changes. Vertebrates differ in their neurogenic and regenerative capacity, being particularly prominent in teleost as adult neurogenesis occurs throughout the rostral-caudal brain axis. This review examines adult proliferation and neurogenesis in the autochthonous Uruguayan teleost Austrolebias charrua and Gymnotus omarorum. A. charrua are annual fishes that live in temporary freshwater pools that dry up in the summer. The luminosity of the puddles varies greatly, and both vision and olfaction are crucial for the survival of this species. G. omarorum inhabits freshwater lagoons and rivers beneath dense masses of floating plants and have nocturnal habits. They rely on the electrosensory modality to navigate and communicate with conspecifics. These differences in habitats and predominant sensory modalities are reflected in the distinct brain morphotypes of G. omarorum and A. charrua. While G. omarorum is characterized by the hypertrophy of rhombencephalic cerebellum and electrosensory lateral line lobe, A. charrua has a well-developed olfactory bulb, mesencephalic tectum opticum, and torus longitudinalis. Accordingly, these regions have notorious neurogenic activity. Differences in neuroanatomy and distribution of neurogenesis in the brains of both species are discussed considering their life cycle and lifestyle. The comparison of these results with those reported in other teleost and vertebrates contributes to the understanding of the key role of neurogenesis in brain plasticity and evolution.
Taking flight, the use of Drosophila melanogaster for neuroscience research in Uruguay
Neuroscience 2025 May 7:573:104-119
Gonzalo Budelli 1 , María José Ferreiro 2 , Carmen Bolatto 3
1 Unidad Académica de Biofísica, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay. Electronic address: gbudelli@fmed.edu.uy. 2 Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Ministerio de Educación y Cultura (MEC), Montevideo, Uruguay. 3 Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay; Departamento de Neurobiología y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Ministerio de Educación y Cultura (MEC), Montevideo, Uruguay.
DOI: 10.1016/j.neuroscience.2025.03.006
PMID: 40058485
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40058485
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(25)00193-9
Abstract:
The Sociedad de Neurociencias del Uruguay is celebrating its 30th anniversary, sustained by more than a century of neuroscience research in the country. During this time, different approaches and experimental organisms have been incorporated to study diverse aspects of neurobiology. One of these experimental animals, successfully used in a variety of biological fields, is the fruit fly Drosophila melanogaster. Although Drosophila has been a model organism for neuroscience research worldwide for many decades, its use in Uruguay for that purpose is relatively new and just taking flight. In this special issue article, we will describe some of the research lines that are currently using Drosophila for neuroscience studies, questioning a wide range of issues including thermoreception, neurodegenerative diseases such as Parkinson's, screening of bioactive compounds with a neuroprotective effect, and gene/protein function during development of the nervous system. The consolidation of these research lines has been achieved due to unique features of D. melanogaster as an experimental model. We will review the advantages of using Drosophila to study neurobiology and describe some of its useful genetic tools. Advantages such as having powerful genetics, highly conserved disease pathways, a complete connectome, very low comparative costs, easy maintenance, and the support of a collaborative community allowing access to a vast toolkit, all make D. melanogaster an ideal model organism for neuroscientists in countries with low levels of investment in research and development. This review focuses on the strengths and description of useful techniques to study neurobiology using Drosophila, from the perspective of a Latin-American experience.
Neurovascular unit impairment in iron deficiency anemia
Neuroscience 2025 Feb 16:567:56-66
Eugenia Isasi 1 , Silvia Olivera-Bravo 2
1 Unidad Académica de Histología y Embriología, Facultad de Medicina, UdelaR, Montevideo, Uruguay; Departamento de Neurobiología y Neuropatología, IIBCE, MEC, Montevideo, Uruguay. 2 Departamento de Neurobiología y Neuropatología, IIBCE, MEC, Montevideo, Uruguay. Electronic address: solivera@iibce.edu.uy.
DOI: 10.1016/j.neuroscience.2024.12.050
PMID: 39733822
Pubmed: https://pubmed.ncbi.nlm.nih.gov/39733822
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(24)00757-7
Abstract:
Iron is one of the crucial elements for CNS development and function and its deficiency (ID) is the most common worldwide nutrient deficit in the world. Iron deficiency anemia (IDA) in pregnant women and infants is a worldwide health problem due to its high prevalence and its irreversible long-lasting effects on brain development. Even with iron supplementation, IDA during pregnancy and/or breastfeeding can result in irreversible cognitive, motor, and behavioral impairments. The neurovascular unit (NVU) plays an important role in iron transport within the CNS as well as in the blood brain-barrier (BBB) formation and maturation, vasculogenesis/angiogenesis, neurovascular coupling and metabolic waste clearance. In animal models of IDA, significant changes have been observed at the capillary level, including alterations in iron transport, vasculogenesis, astrocyte endfeet, and pericytes. Despite these findings, the role of the NVU in IDA remains poorly understood. This review summarizes the potential effects of ID/IDA on brain development, myelination and neuronal function and discusses the role of NVU cells in iron metabolism, BBB, vasculogenesis/angiogenesis, neurovascular coupling and metabolic waste clearance. Furthermore, it emphasizes the need to view the NVU as a whole and as a potential target for ID/IDA. However, it remains unclear to what extent NVU alterations contribute to neuronal dysfunction, myelination abnormalities, and synaptic disturbances described in IDA.
Mitochondria and astrocyte reactivity: Key mechanism behind neuronal injury
Neuroscience 2025 Feb 16:567:227-234
Patricia Cassina 1 , Ernesto Miquel 2 , Laura Martínez-Palma 2 , Adriana Cassina 3
1 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Electronic address: pcassina@fmed.edu.uy. 2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 Departemento de Bioquímica and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
DOI: 10.1016/j.neuroscience.2024.12.058
PMID: 39788313
Pubmed: https://pubmed.ncbi.nlm.nih.gov/39788313
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(24)00765-6
Abstract:
In this special issue to celebrate the 30th anniversary of the Uruguayan Society for Neuroscience (SNU), we find it pertinent to highlight that research on glial cells in Uruguay began almost alongside the history of SNU and contributed to the understanding of neuron-glia interactions within the international scientific community. Glial cells, particularly astrocytes, traditionally regarded as supportive components in the central nervous system (CNS), undergo notable morphological and functional alterations in response to neuronal damage, a phenomenon referred to as glial reactivity. Among the myriad functions of astrocytes, metabolic support holds significant relevance for neuronal function, given the high energy demand of the nervous system. Although astrocytes are typically considered to exhibit low mitochondrial respiratory chain activity, they possess a noteworthy mitochondrial network. Interestingly, both the morphology and activity of these organelles change following glial reactivity. Despite receiving less attention compared to studies on neuronal mitochondria, recent studies indicate that mitochondria play a crucial role in driving the transition of astrocytes from a quiescent to a reactive state in various neurological disorders. Notably, stimulating mitochondria in astrocytes has been shown to reduce damage associated with the neurodegenerative disease amyotrophic lateral sclerosis. Here, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage. In this review, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage.
2025_Cassina_rev_Mitochondria and astrocyte reactivity-Key mechanism behind neuronal injury.pdf