Glia最新文献

{"title":"Cover Image, Volume 72, Issue 11","authors":"Cong Wang,&nbsp;Jing Dong,&nbsp;Heng Huang,&nbsp;Kegui Zhou,&nbsp;Zhenguo Liu,&nbsp;Richard Milner,&nbsp;Longxuan Li","doi":"10.1002/glia.24413","DOIUrl":"10.1002/glia.24413","url":null,"abstract":"<p>Cover Illustration: Representative images of immunofluorescent staining for glial fibrillary acidic protein (GFAP) (green), Iba-1(red) and DAPI (blue) in cultured primary astrocytes from TREM2-GFAP-knockout mice. Over 95% of the cultured cells were identified as astrocytes and no Iba-1 positive cells (microglia) were observed in the cultures. (See Li, L., et al, https://doi.org/10.1002/glia.24597)\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"C1"},"PeriodicalIF":5.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased sialylation elicits complement-related microglia response and bipolar cell loss in the mouse retina","authors":"German Cuevas-Rios,&nbsp;Tawfik Abou Assale,&nbsp;Jannis Wissfeld,&nbsp;Annemarie Bungartz,&nbsp;Julia Hofmann,&nbsp;Thomas Langmann,&nbsp;Harald Neumann","doi":"10.1002/glia.24613","DOIUrl":"10.1002/glia.24613","url":null,"abstract":"<p>Sialylation plays an important role in self-recognition, as well as keeping the complement and innate immune systems in check. It is unclear whether the reduced sialylation seen during aging and in mice heterozygous for the null mutant of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (Gne+/−), an essential enzyme for sialic acid biosynthesis, contributes to retinal inflammation and degeneration. We found a reduction of polysialic acid and trisialic acid expression in several retinal layers in Gne+/− mice at 9 months of age compared to Gne+/+ wildtype (WT) mice, which was associated with a higher microglial expression of the lysosomal marker CD68. Furthermore, the total number of rod bipolar cells was reduced in 12 months old Gne+/− mice in comparison to WT mice, demonstrating loss of these retinal interneurons. Transcriptome analysis showed up-regulation of complement, inflammation, and apoptosis-related pathways in the retinas of Gne+/− mice. Particularly, increased gene transcript levels of the complement factors <i>C3</i> and <i>C4</i> and the pro-inflammatory cytokine <i>Il-1β</i> were observed by semi-quantitative real-time polymerase chain reaction (sqRT-PCR) in 9 months old Gne+/− mice compared to WT mice. The increased expression of CD68, loss of rod bipolar cells, and increased gene transcription of complement factor <i>C4</i>, were all prevented after crossing Gne+/− mice with complement factor <i>C3</i>-deficient animals. In conclusion, our data show that retinal hyposialylation in 9 and 12 months old Gne+/− mice was associated with complement-related inflammation and lysosomal microglia response, as well as rod bipolar cells loss, which was absent after genetic deletion of complement factor C3.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2295-2312"},"PeriodicalIF":5.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferritin loss in astrocytes reduces spinal cord oxidative stress and demyelination in the experimental autoimmune encephalomyelitis (EAE) model","authors":"Z. Smith,&nbsp;V. T. Cheli,&nbsp;C. G. Angeliu,&nbsp;C. Wang,&nbsp;G. E. Denaroso,&nbsp;S. G. Tumuluri,&nbsp;J. Corral,&nbsp;K. Garbarini,&nbsp;P. M. Paez","doi":"10.1002/glia.24616","DOIUrl":"10.1002/glia.24616","url":null,"abstract":"<p>Demyelinating diseases such as multiple sclerosis (MS) cause myelin degradation and oligodendrocyte death, resulting in the release of toxic iron and iron-induced oxidative stress. Astrocytes have a large capacity for iron transport and storage, however the role of astrocytic iron homeostasis in demyelinating disorders is not completely understood. Here we investigate whether astrocytic iron metabolism modulates neuroinflammation, oligodendrocyte survival, and oxidative stress following demyelination. To this aim, we conditionally knock out ferritin in astrocytes and induce experimental autoimmune encephalomyelitis (EAE), an autoimmune-mediated model of demyelination. Ferritin ablation in astrocytes reduced the severity of disease in both the acute and chronic phases. The day of onset, peak disease severity, and cumulative clinical score were all significantly reduced in ferritin KO animals. This corresponded to better performance on the rotarod and increased mobility in ferritin KO mice. Furthermore, the spinal cord of ferritin KO mice display decreased numbers of reactive astrocytes, activated microglia, and infiltrating lymphocytes. Correspondingly, the size of demyelinated lesions, iron accumulation, and oxidative stress were attenuated in the CNS of ferritin KO subjects, particularly in white matter regions of the spinal cord. Thus, deleting ferritin in astrocytes reduced neuroinflammation, oxidative stress, and myelin deterioration in EAE animals. Collectively, these findings suggest that iron storage in astrocytes is a potential therapeutic target to lessen CNS inflammation and myelin loss in autoimmune demyelinating diseases.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2327-2343"},"PeriodicalIF":5.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124370","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}

{"title":"Neuronal and glial cell alterations involved in the retinal degeneration of the familial dysautonomia optic neuropathy","authors":"Anastasia Schultz,&nbsp;Henar Albertos-Arranz,&nbsp;Xavier Sánchez Sáez,&nbsp;Jamie Morgan,&nbsp;Diane C. Darland,&nbsp;Alejandra Gonzalez-Duarte,&nbsp;Horacio Kaufmann,&nbsp;Carlos E. Mendoza-Santiesteban,&nbsp;Nicolás Cuenca,&nbsp;Frances Lefcort","doi":"10.1002/glia.24612","DOIUrl":"10.1002/glia.24612","url":null,"abstract":"<p>Familial dysautonomia (FD) is a rare genetic neurodevelopmental and neurodegenerative disorder. In addition to the autonomic and peripheral sensory neuropathies that challenge patient survival, one of the most debilitating symptoms affecting patients' quality of life is progressive blindness resulting from the steady loss of retinal ganglion cells (RGCs). Within the FD community, there is a concerted effort to develop treatments to prevent the loss of RGCs. However, the mechanisms underlying the death of RGCs are not well understood. To study the mechanisms underlying RGC death, <i>Pax6-cre;Elp1</i>^{<i>loxp/loxp</i>} male and female mice and postmortem retinal tissue from an FD patient were used to explore the neuronal and non-neuronal cellular pathology associated with the FD optic neuropathy. Neurons, astrocytes, microglia, Müller glia, and endothelial cells were investigated using a combination of histological analyses. We identified a novel disruption of cellular homeostasis and gliosis in the FD retina. Beginning shortly after birth and progressing with age, the FD retina is marked by astrogliosis and perturbations in microglia, which coincide with vascular remodeling. These changes begin before the onset of RGC death, suggesting alterations in the retinal neurovascular unit may contribute to and exacerbate RGC death. We reveal for the first time that the FD retina pathology includes reactive gliosis, increased microglial recruitment to the ganglion cell layer (GCL), disruptions in the deep and superficial vascular plexuses, and alterations in signaling pathways. These studies implicate the neurovascular unit as a disease-modifying target for therapeutic interventions in FD.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2268-2294"},"PeriodicalIF":5.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNAJB6 is expressed in neurons and oligodendrocytes of the human brain","authors":"Jónvá Hentze,&nbsp;Jonas Folke,&nbsp;Susana Aznar,&nbsp;Pia Nyeng,&nbsp;Tomasz Brudek,&nbsp;Christian Hansen","doi":"10.1002/glia.24615","DOIUrl":"10.1002/glia.24615","url":null,"abstract":"<p>DNAJB6 is a suppressor of α-synuclein aggregation <i>in vivo</i> and <i>in vitro</i>. DNAJB6 is strongly expressed in the brain, and its overall protein expression is altered in neurodegenerative conditions such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA). These two diseases are characterized by accumulation of aggregated α-synuclein in neurons and oligodendrocytes, respectively. To further explore this, we employed <i>post-mortem</i> normal human brain material to investigate the regional and cell type specific protein expression of DNAJB6. We found that the DNAJB6 protein is ubiquitously expressed across various regions of the brain. Notably, we demonstrate for the first time that DNAJB6 is present in nearly half (41%–53%) of the oligodendrocyte population and in the majority (68%–80%) of neurons. However, DNAJB6 was only sparsely present in other cell types such as astrocytes and microglia. Given that α-synuclein aggregation in oligodendrocytes is a hallmark of MSA, we investigated DNAJB6 presence in MSA brains compared to control brains. We found no significant difference in the percentage of oligodendrocytes where DNAJB6 was present in MSA brains relative to control brains. In conclusion, our results reveal an expression of the DNAJB6 protein across various regions of the human brain, and that DNAJB6 is almost exclusively present in neurons and oligodendrocytes. Since prior studies have shown that PD and MSA brains have altered levels of DNAJB6 relative to control brains, DNAJB6 may be an interesting target for drug development.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2313-2326"},"PeriodicalIF":5.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124369","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}

{"title":"Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination","authors":"Emma R. Wilson,&nbsp;Gustavo Della-Flora Nunes,&nbsp;Shichen Shen,&nbsp;Seth Moore,&nbsp;Joseph Gawron,&nbsp;Jessica Maxwell,&nbsp;Umair Syed,&nbsp;Edward Hurley,&nbsp;Meghana Lanka,&nbsp;Jun Qu,&nbsp;Laurent Désaubry,&nbsp;Lawrence Wrabetz,&nbsp;Yannick Poitelon,&nbsp;M. Laura Feltri","doi":"10.1002/glia.24610","DOIUrl":"10.1002/glia.24610","url":null,"abstract":"<p>Schwann cells are critical for the proper development and function of the peripheral nervous system (PNS), where they form a collaborative relationship with axons. Past studies highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (<i>Phb2</i>) in vivo results in severe defects in radial sorting and myelination. We show in vivo that <i>Phb2</i>-null Schwann cells cannot effectively proliferate and the transcription factors EGR2 (KROX20), POU3F1 (OCT6), and POU3F2 (BRN2), necessary for proper Schwann cell maturation, are dysregulated. Schwann cell-specific deletion of <i>Jun</i>, a transcription factor associated with negative regulation of myelination, confers partial rescue of the developmental defect seen in mice lacking Schwann cell <i>Phb2</i>. Finally, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on neuronal signals, and thus are potential mediators of PHB2-associated developmental defects. This work develops our understanding of Schwann cell biology, revealing that <i>Phb2</i> may modulate the timely expression of transcription factors necessary for proper PNS development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2247-2267"},"PeriodicalIF":5.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102646","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}

{"title":"Astrocytic Ca2+ activation by chemogenetics mitigates the effect of kainic acid-induced excitotoxicity on the hippocampus","authors":"Nira Hernández-Martín,&nbsp;María Gómez Martínez,&nbsp;Pablo Bascuñana,&nbsp;Rubén Fernández de la Rosa,&nbsp;Luis García-García,&nbsp;Francisca Gómez,&nbsp;Maite Solas,&nbsp;Eduardo D. Martín,&nbsp;Miguel A. Pozo","doi":"10.1002/glia.24607","DOIUrl":"10.1002/glia.24607","url":null,"abstract":"<p>Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[¹⁸F]-fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry. Astrocytic Ca²⁺ activation increased the ¹⁸F-FDG uptake, but this effect was not found when the study was performed in <i>knock out</i> mice for type-2 inositol 1,4,5-trisphosphate receptor (Ip3r2^−/−) nor in <i>floxed</i> mice to abolish glucose transporter 1 (GLUT1) expression in hippocampal astrocytes (GLUT1^ΔGFAP). Sustained astrocyte activation after KA injection reversed the brain glucose hypometabolism, restored hippocampal function, prevented neuronal death, and increased hippocampal GABA levels. The findings of our study indicate that astrocytic GLUT1 function is crucial for regulating brain glucose metabolism. Astrocytic Ca²⁺ activation has been shown to promote adaptive changes that significantly contribute to mitigating the effects of KA-induced damage. This evidence suggests a protective role of activated astrocytes against KA-induced excitotoxicity.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2217-2230"},"PeriodicalIF":5.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelin-1 increases Na+-K+-2Cl− cotransporter-1 expression in cultured astrocytes and in traumatic brain injury model: An involvement of HIF1α activation","authors":"Yutaka Koyama,&nbsp;Yasuhiro Hamada,&nbsp;Yura Fukui,&nbsp;Nami Hosogi,&nbsp;Rina Fujimoto,&nbsp;Shigeru Hishinuma,&nbsp;Yasuhiro Ogawa,&nbsp;Kenta Takahashi,&nbsp;Yasuhiko Izumi,&nbsp;Shotaro Michinaga","doi":"10.1002/glia.24609","DOIUrl":"10.1002/glia.24609","url":null,"abstract":"<p>Na⁺-K⁺-2Cl⁻ cotransporter-1 (NKCC1) is present in brain cells, including astrocytes. The expression of astrocytic NKCC1 increases in the acute phase of traumatic brain injury (TBI), which induces brain edema. Endothelin-1 (ET-1) is a factor that induces brain edema and regulates the expression of several pathology-related genes in astrocytes. In the present study, we investigated the effect of ET-1 on NKCC1 expression in astrocytes. ET-1 (100 nM)-treated cultured astrocytes showed increased NKCC1 mRNA and protein levels. The effect of ET-1 on NKCC1 expression in cultured astrocytes was reduced by BQ788 (1 μM), an ET_B antagonist, but not by FR139317 (1 μM), an ET_A antagonist. The involvement of ET-1 in NKCC1 expression in TBI was examined using a fluid percussion injury (FPI) mouse model that replicates the pathology of TBI with high reproducibility. Administration of BQ788 (15 nmol/day) decreased FPI-induced expressions of NKCC1 mRNA and protein, accompanied with a reduction of astrocytic activation. FPI-induced brain edema was attenuated by BQ788 and NKCC1 inhibitors (azosemide and bumetanide). ET-1-treated cultured astrocytes showed increased mRNA and protein expression of hypoxia-inducible factor-1α (HIF1α). Immunohistochemical observations of mouse cerebrum after FPI showed co-localization of HIF1α with GFAP-positive astrocytes. Increased HIF1α expression in the TBI model was reversed by BQ788. FM19G11 (an HIF inhibitor, 1 μM) and HIF1α siRNA suppressed ET-induced increase in NKCC1 expression in cultured astrocytes. These results indicate that ET-1 increases NKCC1 expression in astrocytes through the activation of HIF1α.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2231-2246"},"PeriodicalIF":5.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007950","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}

{"title":"Identification of astrocyte-like cells in an adult ascidian during regeneration of the central nervous system","authors":"Bianca Nicole Santos Paes Medina,&nbsp;Taynan Motta Portal,&nbsp;Carlos Augusto Borges de Andrade Gomes,&nbsp;Rodrigo Nunes-da-Fonseca,&nbsp;Silvana Allodi,&nbsp;Cintia Monteiro-de-Barros","doi":"10.1002/glia.24605","DOIUrl":"10.1002/glia.24605","url":null,"abstract":"<p>The mechanisms underlying regeneration of the central nervous system (CNS) following lesions have been studied extensively in both vertebrate and invertebrate models. To shed light on regeneration, ascidians, a sister group of vertebrates and with remarkable ability to regenerate their brains, constitute an appropriate model system. Glial cells have been implicated in regeneration in vertebrates; however, their role in the adult ascidian CNS regeneration is unknown. A model of degeneration and regeneration using the neurotoxin 3-acetylpyridine (3AP) in the brain of the ascidian <i>Styela plicata</i> was used to identify astrocyte-like cells and investigate their role. We studied the CNS of control ascidians (injected with artificial sea water) and of ascidians whose CNS was regenerating (1 and 10 days after the injection with 3AP). Our results show that the mRNA of the ortholog of glutamine synthetase (GS), a glial-cell marker in vertebrates, is increased during the early stages of regeneration. Confirming the identity of GS, the protein was identified via immunostaining in a cell population during the same regeneration stage. Last, a single ortholog of GS (GSII) is present in ascidian and amphioxus genomes, while two types exist in fungi, some invertebrates, and vertebrates, suggesting that ascidians have lost the GSI type. Taken together, our findings revealed that a cell population expressing glial-cell markers may play a role in regeneration in adult ascidians. This is the first report of astrocyte-like cells in the adult ascidian CNS, and contributes to understanding of the evolution of glial cells among metazoans.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2190-2200"},"PeriodicalIF":5.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994845","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}

{"title":"Schwann cell JUN expression worsens motor performance in an amyotrophic lateral sclerosis mouse model","authors":"Sonia Cabeza-Fernández,&nbsp;Rubí Hernández-Rojas,&nbsp;Angeles Casillas-Bajo,&nbsp;Nikiben Patel,&nbsp;Alerie G. de la Fuente,&nbsp;Hugo Cabedo,&nbsp;Jose A. Gomez-Sanchez","doi":"10.1002/glia.24604","DOIUrl":"10.1002/glia.24604","url":null,"abstract":"<p>Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by motor neuron death and distal axonopathy. Despite its clinical severity and profound impact in the patients and their families, many questions about its pathogenesis remain still unclear, including the role of Schwann cells and axon-glial signaling in disease progression. Upon axonal injury, upregulation of JUN transcription factor promotes Schwann cell reprogramming into a repair phenotype that favors axon regrowth and neuronal survival. To study the potential role of repair Schwann cells on motoneuron survival in amyotrophic lateral sclerosis, we generated a mouse line that over-expresses JUN in the Schwann cells of the SOD1^G93A mutant, a mouse model of this disease. Then, we explored disease progression by evaluating survival, motor performance and histology of peripheral nerves and spinal cord of these mice. We found that Schwann cell JUN overexpression does not prevent axon degeneration neither motor neuron death in the SOD1^G93A mice. Instead, it induces a partial demyelination of medium and large size axons, worsening motor performance and resulting in more aggressive disease phenotype.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 12","pages":"2178-2189"},"PeriodicalIF":5.4,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}