Glia最新文献 - Book学术

Targeting Connexin 43 in Retinal Astrocytes Promotes Neuronal Survival in Glaucomatous Injury.

IF 5.4 2区医学

Glia Pub Date : 2025-03-28 DOI: 10.1002/glia.70013

Khulan Batsuuri, Abduqodir H Toychiev, Suresh Viswanathan, Stefanie G Wohl, Miduturu Srinivas

{"title":"Targeting Connexin 43 in Retinal Astrocytes Promotes Neuronal Survival in Glaucomatous Injury.","authors":"Khulan Batsuuri, Abduqodir H Toychiev, Suresh Viswanathan, Stefanie G Wohl, Miduturu Srinivas","doi":"10.1002/glia.70013","DOIUrl":"https://doi.org/10.1002/glia.70013","url":null,"abstract":"Astrocytes in the retina and optic nerve head play an important role in the pathogenesis of glaucoma. Astrocytes extensively express connexin 43 (Cx43), a protein that forms gap junction (GJ) channels and transmembrane unopposed hemichannels. While it is well documented that Cx43 expression is augmented in retinal injuries, the role of astrocytic Cx43 channels in glaucomatous injury is not fully understood. Here, we used a mouse model of ocular hypertension caused by intracameral microbead injections and a more severe model, optic nerve crush (ONC) injury, and assessed changes in Cx43 expression and GJ channel function. The effect of astrocyte-specific deletion of Cx43 (Cx43KO) on retinal ganglion cell (RGC) loss and visual function was also assessed. We show that the Cx43 expression is increased in retinal astrocytes at early time points and remained elevated even after sustained elevation of intraocular pressure (IOP) (~8 weeks), which paralleled an increase in astrocytic GJ coupling. Deletion of astrocytic Cx43 markedly improved the survival of RGCs by ~93% and preserved visual function as assessed by ERG and reduced numbers of activated microglial/macrophages in the glaucomatous retina. Cx43 expression was also substantially increased after ONC injury, and the absence of Cx43 in this model increased RGC survival by ~48%. These results reveal a deleterious role for Cx43 in glaucoma progression. Intravitreal injections of Gap19, a peptide that reportedly inhibits Cx43 hemichannels but not GJ channels, markedly increased RGC survival and visual function. Further studies are required to assess whether targeting Cx43 hemichannels might be useful for glaucoma treatment.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Histone Methyltransferases EHMT1 and EHMT2 Repress the Expression of Genes Related to Excitability and Cell Death in Oligodendrocyte Progenitors.

IF 5.4 2区医学

Glia Pub Date : 2025-03-25 DOI: 10.1002/glia.70014

Mathilde Pruvost, Hye-Jin Park, Chloé Habermacher, Meng Li, Maria Cecilia Angulo, Jia Liu, Patrizia Casaccia

{"title":"The Histone Methyltransferases EHMT1 and EHMT2 Repress the Expression of Genes Related to Excitability and Cell Death in Oligodendrocyte Progenitors.","authors":"Mathilde Pruvost, Hye-Jin Park, Chloé Habermacher, Meng Li, Maria Cecilia Angulo, Jia Liu, Patrizia Casaccia","doi":"10.1002/glia.70014","DOIUrl":"https://doi.org/10.1002/glia.70014","url":null,"abstract":"Oligodendrocyte progenitor cells (OPCs) represent a population of electrically active and dividing cells, which are capable of responding to neuronal activity by proliferating and differentiating. Here, we report that the repressive euchromatic H3K9me2 histone mark, deposited by the histone methyltransferases EHMT1 and EHMT2 enzymes, increases in proliferating OPCs in mice following optogenetic stimulation of neuronal activity. Using primary cultured OPCs with genetic deletion of Ehmt1 and Ehmt2, and pharmacological inhibition of EHMT enzymatic activity, we reveal the importance of these enzymes in repressing the expression of genes regulating cell death and electrical properties in proliferating OPCs. Consistent with these findings, we detect higher levels of cholinergic muscarinic receptors, fewer numbers of oligodendrocyte lineage cells, and lower levels of the myelin basic protein (MBP) in mice with lineage-specific ablation of Ehmt1 and Ehmt2. Together these data suggest that the repressive H3K9me2 histone mark, whose levels increase in proliferating OPCs after neuronal stimulation, is an important modulator of cell death and proteins regulating the electrical properties of OPCs.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hippocampal Astrocyte Morphology Follows an Unexpected Trajectory With Age in a Transgenic Rodent Model of Tauopathy.

IF 5.4 2区医学

Glia Pub Date : 2025-03-22 DOI: 10.1002/glia.70019

Emma Augustin, Tatiana Vinasco-Sandoval, Miriam Riquelme-Perez, Damien Plassard, Mylène Gaudin, Gwenaëlle Aurégan, Julien Mitja, Sueva Bernier, Charlène Joséphine, Fanny Petit, Caroline Jan, Anne-Sophie Hérard, Marie-Claude Gaillard, Agathe Launay, Emilie Faivre, Luc Buée, Anne-Laurence Boutillier, David Blum, Alexis-Pierre Bemelmans, Gilles Bonvento, Karine Cambon

{"title":"Hippocampal Astrocyte Morphology Follows an Unexpected Trajectory With Age in a Transgenic Rodent Model of Tauopathy.","authors":"Emma Augustin, Tatiana Vinasco-Sandoval, Miriam Riquelme-Perez, Damien Plassard, Mylène Gaudin, Gwenaëlle Aurégan, Julien Mitja, Sueva Bernier, Charlène Joséphine, Fanny Petit, Caroline Jan, Anne-Sophie Hérard, Marie-Claude Gaillard, Agathe Launay, Emilie Faivre, Luc Buée, Anne-Laurence Boutillier, David Blum, Alexis-Pierre Bemelmans, Gilles Bonvento, Karine Cambon","doi":"10.1002/glia.70019","DOIUrl":"https://doi.org/10.1002/glia.70019","url":null,"abstract":"Individual protoplasmic astrocytes have very complex and diverse spongiform shapes. The morphological diversity of astrocytes is determined by the structural and functional interactions of the astrocyte with its microenvironment. When faced with pathological conditions, astrocytes reorganize their morphology. Yet, little is known about the astrocytic response in pure tauopathies and its evolution over time. Here, we aimed to investigate the consequences of a primary neuronal tau pathology on astrocyte fine morphology at three stages of the disease using the transgenic Thy-Tau22 mouse model. We first showed that hippocampal astrocytes in Thy-Tau22 mice progressively accumulate hyperphosphorylated tau with age. We then developed a pipeline of analyses, including 3D reconstruction of hippocampal tdTomato-labeled astrocytes via a PHP.eB adeno-associated virus, confocal microscopy, Imaris software morphometric analysis, and an advanced statistical analysis. During normal aging, the complexity of astrocyte morphology peaked at adulthood, then declined. In contrast, in Thy-Tau22 mice, tauopathy was associated with a simpler initial morphology, followed by the appearance of a cluster of complex cells at the most advanced stage. Using principal component analysis and hierarchical clustering based on 10 morphological features, we were able to identify different astrocyte morphotypes whose relative proportion varies differently with age between WT and Thy-Tau22 mice. Interestingly, we revealed that a fraction of astrocytes with a complex morphology re-emerges late in tauopathy-affected animals. Our data highlight the concept of significant and reversible structural plasticity of astrocytes when faced with chronic pathological conditions.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disruption of Oligodendroglial Autophagy Leads to Myelin Morphological Deficits, Neuronal Apoptosis, and Cognitive Decline in Aged Mice.

IF 5.4 2区医学

Glia Pub Date : 2025-03-19 DOI: 10.1002/glia.70012

Niki Ktena, Dimitrios Spyridakos, Alexandros Georgilis, Ilias Kalafatakis, Efstathia Thomoglou, Angeliki Kolaxi, Vassiliki Nikoletopoulou, Maria Savvaki, Domna Karagogeos

{"title":"Disruption of Oligodendroglial Autophagy Leads to Myelin Morphological Deficits, Neuronal Apoptosis, and Cognitive Decline in Aged Mice.","authors":"Niki Ktena, Dimitrios Spyridakos, Alexandros Georgilis, Ilias Kalafatakis, Efstathia Thomoglou, Angeliki Kolaxi, Vassiliki Nikoletopoulou, Maria Savvaki, Domna Karagogeos","doi":"10.1002/glia.70012","DOIUrl":"https://doi.org/10.1002/glia.70012","url":null,"abstract":"The aging central nervous system (CNS) is often marked by myelin degeneration, yet the underlying mechanisms remain elusive. This study delves into the previously unexplored role of autophagy in maintaining CNS myelin during aging. We generated the transgenic mouse line plpCreERT2; atg5f/f, enabling selective deletion of the core autophagic component Atg5 in oligodendrocytes (OLs) following tamoxifen administration in adulthood, while analysis was conducted on aged mice. Our findings reveal that oligodendroglial autophagy inactivation leads to significant alterations in myelin protein levels. Moreover, the ultrastructural analysis revealed pronounced myelin deficits and increased degeneration of axons, accompanied by apoptosis, as confirmed by immunohistochemistry. Behaviorally, aged knockout (cKO) mice exhibited marked deficits in learning and memory tasks, indicative of cognitive impairment. Additionally, we observed increased activation of microglia, suggesting an inflammatory response linked to the absence of autophagic activity in OLs. These results underscore the critical role of autophagy in OLs for the preservation of CNS myelin and axonal integrity during aging. Our study highlights autophagy as a vital mechanism for neural maintenance, offering potential therapeutic avenues for combating age-related neurodegenerative diseases.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibroblasts and hiPS-Derived Astrocytes From CoPAN Patients Showed Different Levels of Iron Overload Correlated With Senescent Phenotype.

IF 5.4 2区医学

Glia Pub Date : 2025-03-19 DOI: 10.1002/glia.70017

Anna Cozzi, Paolo Santambrogio, Andrea Stefano Moro, Alessio Pelagatti, Alicia Rubio, Chiara Balestrucci, Ivano Di Meo, Valeria Tiranti, Sonia Levi

{"title":"Fibroblasts and hiPS-Derived Astrocytes From CoPAN Patients Showed Different Levels of Iron Overload Correlated With Senescent Phenotype.","authors":"Anna Cozzi, Paolo Santambrogio, Andrea Stefano Moro, Alessio Pelagatti, Alicia Rubio, Chiara Balestrucci, Ivano Di Meo, Valeria Tiranti, Sonia Levi","doi":"10.1002/glia.70017","DOIUrl":"https://doi.org/10.1002/glia.70017","url":null,"abstract":"COASY protein-associated neurodegeneration (CoPAN) is a rare autosomal recessive disorder within the Neurodegeneration with Brain Iron Accumulation spectrum, resulting from mutations in COASY. This gene encodes the bifunctional enzyme essential for the final steps of coenzyme A biosynthesis. To elucidate the pathophysiology and iron dyshomeostasis underlying CoPAN, we analyzed fibroblasts and human induced pluripotent stem (hiPS)-derived astrocytes from two patients carrying distinct COASY mutations. Our findings reveal that CoPAN fibroblasts display altered iron homeostasis, characterized by iron aggregates, elevated cytosolic labile iron pool, and impaired tubulin acetylation. Patients hiPS-derived astrocytes showed mitochondrial morphological abnormalities and compromised vesicular trafficking. Notably, both cell types demonstrated evidence of ferroptosis, but the astrocytes exhibited more pronounced iron accumulation and lipid peroxidation. These results demonstrate that astrocytes may more accurately recapitulate the pathological phenotype of CoPAN compared to fibroblasts. Interestingly, astrocytes exhibited different levels of iron accumulation concomitant with cellular senescence, indicating a possible role of iron-induced cellular senescence. This finding suggests that the accumulation of cytosolic iron, possibly caused by mitochondrial dysfunction, actively promotes senescence. Our data emphasize the potential therapeutic efficacy of drugs that enhance mitochondrial functionality to attenuate the effects of CoPAN.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The X-Linked Intellectual Disability Gene, ZDHHC9, Is Important for Oligodendrocyte Subtype Determination and Myelination.

IF 5.4 2区医学

Glia Pub Date : 2025-03-19 DOI: 10.1002/glia.70016

Rocio B White, Angela R Wild, Timothy P O'Leary, Andrew J Thompson, Stephane Flibotte, Angie Peng, Jason C Rogalski, Mila Mair, Neeki Derhami, Shernaz X Bamji

{"title":"The X-Linked Intellectual Disability Gene, ZDHHC9, Is Important for Oligodendrocyte Subtype Determination and Myelination.","authors":"Rocio B White, Angela R Wild, Timothy P O'Leary, Andrew J Thompson, Stephane Flibotte, Angie Peng, Jason C Rogalski, Mila Mair, Neeki Derhami, Shernaz X Bamji","doi":"10.1002/glia.70016","DOIUrl":"https://doi.org/10.1002/glia.70016","url":null,"abstract":"Two percent of patients with X-linked intellectual disability (XLID) exhibit loss-of-function mutations in the enzyme, ZDHHC9. One of the main anatomical deficits observed in these patients is a decrease in corpus callosum volume and a concurrent disruption in white matter integrity. In this study, we demonstrate that deletion of Zdhhc9 in mice disrupts the balance of mature oligodendrocyte subtypes within the corpus callosum. While overall mature oligodendrocyte numbers are unchanged, there is a marked increase in MOL5/6 cells that are enriched in genes associated with cell adhesion and synapses, and a concomitant decrease in MOL2/3 cells that are enriched in genes associated with myelination. In line with this, we observed a decrease in the density of myelinated axons and disruptions in myelin compaction in the corpus callosum of Zdhhc9 knockout mice. RNA sequencing and proteomic analysis further revealed a reduction in genes and proteins essential for lipid metabolism, cholesterol synthesis, gene expression, and myelin compaction, offering insights into the underlying mechanisms of the pathology. These findings reveal a previously underappreciated and fundamental role for ZDHHC9 and protein palmitoylation in regulating oligodendrocyte subtype determination and myelinogenesis, offering mechanistic insights into the deficits observed in white matter volume in patients with mutations in ZDHHC9.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover Image, Volume 73, Issue 5

IF 5.4 2区医学

Glia Pub Date : 2025-03-18 DOI: 10.1002/glia.24552

Helmut Kettenmann, Bilge Ugursu, Bruce R. Ransom, Christian Steinhäuser

引用次数: 0

Cholinergic and Glutamatergic Axons Differentially Require Glial Support in the Drosophila PNS.

IF 5.4 2区医学

Glia Pub Date : 2025-03-17 DOI: 10.1002/glia.70011

Steffen Kautzmann, Simone Rey, Amber Krebs, Christian Klämbt

{"title":"Cholinergic and Glutamatergic Axons Differentially Require Glial Support in the Drosophila PNS.","authors":"Steffen Kautzmann, Simone Rey, Amber Krebs, Christian Klämbt","doi":"10.1002/glia.70011","DOIUrl":"https://doi.org/10.1002/glia.70011","url":null,"abstract":"In vertebrates, there is a differential interaction between peripheral axons and their associated glial cells. While large-caliber axons are covered by a myelin sheath, small-diameter axons are simply wrapped in Remak fibers. In peripheral nerves of Drosophila larvae, axons are covered by wrapping glial cell processes similar to vertebrate Remak fibers. Whether differences in axonal diameter influence the interaction with glial processes in Drosophila has not yet been analyzed. Likewise, it is not understood whether the modality of the neuron affects the interaction with the wrapping glia. To start to decipher the mechanisms underlying glial wrapping, we employed APEX2 labeling in larval filet preparations. This allowed us to follow individual axons of defined segmental nerves at ultrastructural resolution in the presence or absence of wrapping glia. Using these tools, we first demonstrate that motor axons are larger compared to sensory axons. Sensory axons fasciculate in larger groups than motor axons, suggesting that they do not require direct contact with wrapping glia. However, unlike motor axons, sensory axons show length-dependent degeneration upon ablation of wrapping glia. These data suggest that Drosophila may help to understand peripheral neuropathies caused by defects in Schwann cell function, in which a similar degeneration of sensory axons is observed.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amyloid-β Dysregulates Oligodendroglial Lineage Cell Dynamics and Myelination via PKC in the Zebrafish Spinal Cord.

IF 5.4 2区医学

Glia Pub Date : 2025-03-14 DOI: 10.1002/glia.70015

Uxue Balantzategi, Adhara Gaminde-Blasco, Christina A Kearns, Laura Bayón-Cordero, María Victoria Sánchez-Gómez, José Luis Zugaza, Bruce Appel, Elena Alberdi

{"title":"Amyloid-β Dysregulates Oligodendroglial Lineage Cell Dynamics and Myelination via PKC in the Zebrafish Spinal Cord.","authors":"Uxue Balantzategi, Adhara Gaminde-Blasco, Christina A Kearns, Laura Bayón-Cordero, María Victoria Sánchez-Gómez, José Luis Zugaza, Bruce Appel, Elena Alberdi","doi":"10.1002/glia.70015","DOIUrl":"https://doi.org/10.1002/glia.70015","url":null,"abstract":"Soluble forms of amyloid-β (Aβ) peptide have been proposed as candidates to induce oligodendrocyte (OL) and myelin dysfunctions in the early stages of Alzheimer's disease (AD) pathology. Nevertheless, little is known about how Aβ affects OL differentiation and myelination in vivo, and the underlying molecular mechanisms. In this study, we explored the effects of a brain intraventricular injection of Aβ on OLs and myelin in the developing spinal cord of zebrafish larvae. Using quantitative fluorescent in situ RNA hybridization assays, we demonstrated that Aβ altered myrf and mbp mRNA levels and the regional distribution of mbp during larval development, suggesting an early differentiation of OLs. Through live imaging of Tg(myrf:mScarlet) and Tg(mbpa:tagRFP) zebrafish lines, both crossed with Tg(olig2:EGFP), we found that Aβ increased the number of myrf+ and mbp+ OLs in the dorsal spinal cord at 72 hpf and 5 dpf, respectively, without affecting total cell numbers. Furthermore, Aβ also increased the number of Sox10+cells, myelin sheaths per OL, and the number of myelinated axons in the dorsal spinal cord at 8 dpf compared to vehicle-injected control animals. Interestingly, the treatment of Aβ-injected zebrafish with the pan-PKC inhibitor Gö6983 restored the aforementioned alterations in OLs and myelin to control levels. Altogether, not only do we demonstrate that Aβ induces a precocious oligodendroglial differentiation leading to dysregulated myelination, but we also identified PKC as a key player in Aβ-induced pathology.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Temporal Profiling of Male Cortical Astrocyte Transcription Predicts Molecular Shifts From Early Development to Aging.

IF 5.4 2区医学

Glia Pub Date : 2025-03-13 DOI: 10.1002/glia.70010

Xiaoran Wei, Jiangtao Li, Michelle L Olsen

{"title":"Temporal Profiling of Male Cortical Astrocyte Transcription Predicts Molecular Shifts From Early Development to Aging.","authors":"Xiaoran Wei, Jiangtao Li, Michelle L Olsen","doi":"10.1002/glia.70010","DOIUrl":"https://doi.org/10.1002/glia.70010","url":null,"abstract":"Astrocytes are the most abundant glial cell type in the central nervous system (CNS). Astrocytes are born during the early postnatal period in the rodent brain and mature alongside neurons, demonstrating remarkable morphological structural complexity, which is attained in the second postnatal month. Throughout this period of development and across the remainder of the lifespan, astrocytes participate in CNS homeostasis, support neuronal partners, and contribute to nearly all aspects of CNS function. In the present study, we analyzed astrocyte gene expression in the cortex of wild-type male rodents throughout their lifespan (postnatal 7 days to 18 months). A pairwise timepoint comparison of differential gene expression during early development and CNS maturation (7-60 days) revealed four unique astrocyte gene clusters, each with hundreds of genes, which demonstrate unique temporal profiles. These clusters are distinctively related to cell division, cell morphology, cellular communication, and vascular structure and regulation. A similar analysis across adulthood and in the aging brain (3 to 18 months) identified similar patterns of grouped gene expression related to cell metabolism and cell structure. Additionally, our analysis identified that during the aging process astrocytes demonstrate a bias toward shorter transcripts, with loss of longer genes related to synapse development and a significant increase in shorter transcripts related to immune regulation and the response to DNA damage. Our study highlights the critical role that astrocytes play in maintaining CNS function throughout life and reveals molecular shifts that occur during development and aging in the cortex of male mice.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0