Glia最新文献

{"title":"Astrocyte-derived factors regulate CNS myelination","authors":"Sybille Seiler,&nbsp;Franziska Rudolf,&nbsp;Filipa Ramilo Gomes,&nbsp;Anto Pavlovic,&nbsp;Jana Nebel,&nbsp;Constanze I. Seidenbecher,&nbsp;Lynette C. Foo","doi":"10.1002/glia.24596","DOIUrl":"10.1002/glia.24596","url":null,"abstract":"<p>The role that astrocytes play in central nervous system (CNS) myelination is poorly understood. We investigated the contribution of astrocyte-derived factors to myelination and revealed a substantial overlap in the secretomes of human and rat astrocytes. Using in vitro myelinating co-cultures of primary retinal ganglion cells and cortical oligodendrocyte precursor cells, we discovered that factors secreted by resting astrocytes, but not reactive astrocytes, facilitated myelination. Soluble brevican emerged as a new enhancer of developmental myelination in vivo, CNS and its absence was linked to remyelination deficits following an immune-mediated damage in an EAE mouse model. The observed reduction of brevican expression in reactive astrocytes and human MS lesions suggested a potential link to the compromised remyelination characteristic of neurodegenerative diseases. Our findings suggested brevican's role in myelination may be mediated through interactions with binding partners such as contactin-1 and tenascin-R. Proteomic analysis of resting versus reactive astrocytes highlighted a shift in protein expression profiles, pinpointing candidates that either facilitate or impede CNS repair, suggesting that depending on their reactivity state, astrocytes play a dual role during myelination.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"2038-2060"},"PeriodicalIF":5.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877283","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":"Adenosine A2B receptors differently modulate oligodendrogliogenesis and myelination depending on their cellular localization","authors":"Federica Cherchi,&nbsp;Martina Venturini,&nbsp;Giada Magni,&nbsp;Lucia Frulloni,&nbsp;Martina Chieca,&nbsp;Daniela Buonvicino,&nbsp;Clara Santalmasi,&nbsp;Francesca Rossi,&nbsp;Francesco De Logu,&nbsp;Elisabetta Coppi,&nbsp;Anna Maria Pugliese","doi":"10.1002/glia.24593","DOIUrl":"10.1002/glia.24593","url":null,"abstract":"<p>Differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs) is a key event for axonal myelination in the brain; this process fails during demyelinating pathologies. Adenosine is emerging as an important player in oligodendrogliogenesis, by activating its metabotropic receptors (A₁R, A_2AR, A_2BR, and A₃R). We previously demonstrated that the Gs-coupled A_2BR reduced differentiation of primary OPC cultures by inhibiting delayed rectifier (I_K) as well as transient (I_A) outward K⁺ currents. To deepen the unclear role of this receptor subtype in neuron-OL interplay and in myelination process, we tested the effects of different A_2BR ligands in a dorsal root ganglion neuron (DRGN)/OPC cocultures, a corroborated in vitro myelination assay. The A_2BR agonist, BAY60-6583, significantly reduced myelin basic protein levels but simultaneously increased myelination index in DRGN/OPC cocultures analyzed by confocal microscopy. The last effect was prevented by the selective A_2BR antagonists, PSB-603 and MRS1706. To clarify this unexpected data, we wondered whether A_2BRs could play a functional role on DRGNs. We first demonstrated, by immunocytochemistry, that primary DRGN monoculture expressed A_2BRs. Their selective activation by BAY60-6583 enhanced DRGN excitability, as demonstrated by increased action potential firing, decreased rheobase and depolarized resting membrane potential and were prevented by PSB-603. Throughout this A_2BR-dependent enhancement of neuronal activity, DRGNs could release factors to facilitate myelination processes. Finally, silencing A_2BR in DRGNs alone prevents the increased myelination induced by BAY60-6583 in cocultures. In conclusion, our data suggest a different role of A_2BR during oligodendrogliogenesis and myelination, depending on their activation on neurons or oligodendroglial cells.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"1985-2000"},"PeriodicalIF":5.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24593","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791387","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":"Myelin debris phagocytosis in demyelinating disease","authors":"Rui Gao,&nbsp;Sheng-Jiao Song,&nbsp;Meng-Yuan Tian,&nbsp;Li-Bin Wang,&nbsp;Yuan Zhang,&nbsp;Xing Li","doi":"10.1002/glia.24602","DOIUrl":"10.1002/glia.24602","url":null,"abstract":"<p>Demyelinating diseases are often caused by a variety of triggers, including immune responses, viral infections, malnutrition, hypoxia, or genetic factors, all of which result in the loss of myelin in the nervous system. The accumulation of myelin debris at the lesion site leads to neuroinflammation and inhibits remyelination; therefore, it is crucial to promptly remove the myelin debris. Initially, Fc and complement receptors on cellular surfaces were the primary clearance receptors responsible for removing myelin debris. However, subsequent studies have unveiled the involvement of additional receptors, including Mac-2, TAM receptors, and the low-density lipoprotein receptor-related protein 1, in facilitating the removal process. In addition to microglia and macrophages, which serve as the primary effector cells in the disease phase, a variety of other cell types such as astrocytes, Schwann cells, and vascular endothelial cells have been demonstrated to engage in the phagocytosis of myelin debris. Furthermore, we have concluded that oligodendrocyte precursor cells, as myelination precursor cells, also exhibit this phagocytic capability. Moreover, our research group has innovatively identified the low-density lipoprotein receptor as a potential phagocytic receptor for myelin debris. In this article, we discuss the functional processes of various phagocytes in demyelinating diseases. We also highlight the alterations in signaling pathways triggered by phagocytosis, and provide a comprehensive overview of the various phagocytic receptors involved. Such insights are invaluable for pinpointing potential therapeutic strategies for the treatment of demyelinating diseases by targeting phagocytosis.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"1934-1954"},"PeriodicalIF":5.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786627","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":"CD4+ T cell-associated cytokines induce a chronic pro-inflammatory phenotype in induced pluripotent stem cell-derived midbrain astrocytes","authors":"Adina N. MacMahon Copas,&nbsp;Sarah F. McComish,&nbsp;Andreea Petrasca,&nbsp;Rachel McCormack,&nbsp;Daniel Ivers,&nbsp;Anna Stricker,&nbsp;Jean M. Fletcher,&nbsp;Maeve A. Caldwell","doi":"10.1002/glia.24601","DOIUrl":"10.1002/glia.24601","url":null,"abstract":"<p>Astrocytes are mediators of homeostasis but contribute to neuroinflammation in Parkinson's disease (PD). Mounting evidence suggests involvement of peripheral immune cells in PD pathogenesis. Therefore, this study aimed to determine the potential role of peripheral immune secreted cytokines in modulating midbrain astrocyte reactivity. Human iPSC-derived midbrain astrocytes were exposed to 5% and 10% CD4⁺ T cell conditioned media (CD4CM) for 24 h, 72 h, and 7 days to assess chronic exposure. Additionally, astrocytes were exposed to the Th17 cell cytokine, IL-17A (10 ng/mL), alone and in combination with TNF-α (0.3 ng/mL) to assess potential synergistic effects of both cytokines at 24 h, 72 h, and 7 days. CD4CM induced acute and chronic alterations in midbrain astrocytes. Increased NFκB translocation to the nucleus, increased expression of the pro-inflammatory genes, IL-1β, CXCL10 at 24 h, C3, LCN2, IL-6 at 24 and 48 h, as well as an increase in their release of pro-inflammatory cytokines IL-6 and CXCL10 at both these time points were observed. A synergistic response to the combination of IL-17A and TNF-α on increasing inflammatory gene expression and cytokine release occurred. IL-17A and TNF-α increased intensity of S100β at 24 h, decreased nuclear area and increased circularity of astrocytes at 72 h. A synergistic effect on γH2AX intensity at 72 h and an increase in LDH release at 7 days was observed. Our results demonstrate that IL-17A and TNF-α act synergistically, enhancing midbrain astrocyte reactivity to a similar degree as CD4CM. This highlights the importance of the peripheral immune secreted cytokines in increasing the reactivity status of midbrain astrocytes, implicating their role in PD.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"2142-2154"},"PeriodicalIF":5.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755990","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":"Astrocyte-TREM2 alleviates brain injury by regulating reactive astrocyte states following ischemic stroke","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.24597","DOIUrl":"10.1002/glia.24597","url":null,"abstract":"<p>Triggering receptor expressed on myeloid cells 2 (TREM2) has been shown to confer strong neuroprotective effects in acute ischemic stroke (AIS). However, as the vast majority of research findings to date are based on its functions in microglia, the precise role of TREM2 in astrocytes after AIS is unknown. Here, both loss- and gain-of-function experiments were employed to investigate how astrocytic TREM2 influences the pathogenesis of AIS in vivo and in vitro. Our results demonstrated that cerebral ischemia triggered induction of TREM2 expression on reactive astrocytes following AIS. In addition, astrocyte-specific TREM2 knockout mice exhibited much greater brain injury than TREM2 flox/flox controls following AIS, as evidenced by increased cerebral infarct volume, neuronal apoptosis and neurological deficit, which was associated with an increased expression of pro-inflammatory molecule complement component 3 (C3) on reactive astrocytes and activation of microglia/macrophages but decreased expression of S100 calcium binding protein A10 (S100A10) and arginase1 (Arg1) on reactive astrocytes. Mechanistic analyses revealed that astrocytic TREM2 alleviated brain injury by inhibiting detrimental actions of reactive astrocytes but promoting their neuro- and glioprotective actions via the kruppel-like transcription factor-4-nuclear factor-κB axis. Together, this study provides novel evidence for a critical protective role of astrocyte-derived TREM2 in AIS and highlights a potential therapeutic target for the treatment of AIS.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"2061-2078"},"PeriodicalIF":5.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755989","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":"Dysfunctional astrocyte glutamate uptake in the hypothalamic paraventricular nucleus contributes to visceral pain and anxiety-like behavior in mice with chronic pancreatitis","authors":"Rong Luo,&nbsp;Xiaojun Hu,&nbsp;Xin Li,&nbsp;Fan Lei,&nbsp;Ping Liao,&nbsp;Limei Yi,&nbsp;Xia Zhang,&nbsp;Bin Zhou,&nbsp;Ruotian Jiang","doi":"10.1002/glia.24595","DOIUrl":"10.1002/glia.24595","url":null,"abstract":"<p>Abdominal visceral pain is a predominant symptom in patients with chronic pancreatitis (CP); however, the underlying mechanism of pain in CP remains elusive. We hypothesized that astrocytes in the hypothalamic paraventricular nucleus (PVH) contribute to CP pain pathogenesis. A mouse model of CP was established by repeated intraperitoneal administration of caerulein to induce abdominal visceral pain. Abdominal mechanical stimulation, open field and elevated plus maze tests were performed to assess visceral pain and anxiety-like behavior. Fiber photometry, brain slice Ca²⁺ imaging, electrophysiology, and immunohistochemistry were used to investigate the underlying mechanisms. Mice with CP displayed long-term abdominal mechanical allodynia and comorbid anxiety, which was accompanied by astrocyte glial fibrillary acidic protein reactivity, elevated Ca²⁺ signaling, and astroglial glutamate transporter-1 (GLT-1) deficits in the PVH. Specifically, reducing astrocyte Ca²⁺ signaling in the PVH via chemogenetics significantly rescued GLT-1 deficits and alleviated mechanical allodynia and anxiety in mice with CP. Furthermore, we found that GLT-1 deficits directly contributed to the hyperexcitability of VGLUT2^PVH neurons in mice with CP, and that pharmacological activation of GLT-1 alleviated the hyperexcitability of VGLUT2^PVH neurons, abdominal visceral pain, and anxiety in these mice. Taken together, our data suggest that dysfunctional astrocyte glutamate uptake in the PVH contributes to visceral pain and anxiety in mice with CP, highlighting GLT-1 as a potential therapeutic target for chronic pain in patients experiencing CP.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"2022-2037"},"PeriodicalIF":5.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750650","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":"MicroRNA-146a-5p protects retinal ganglion cells through reducing neuroinflammation in experimental glaucoma","authors":"Han Zhou,&nbsp;Rui-Kang Yang,&nbsp;Qian Li,&nbsp;Zhen Li,&nbsp;Yong-Chen Wang,&nbsp;Shu-Ying Li,&nbsp;Yanying Miao,&nbsp;Xing-Huai Sun,&nbsp;Zhongfeng Wang","doi":"10.1002/glia.24600","DOIUrl":"10.1002/glia.24600","url":null,"abstract":"<p>Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA-146 (miR-146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR-146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR-146 family only miR-146a-5p expression was upregulated in COH retinas. The upregulation of miR-146a-5p was observed in the activated microglia and Müller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR-146a-5p in COH retinas reduced the levels pro-inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR-146a-5p mimic increased the percentage of anti-inflammatory phenotype in the activated BV2 microglia, while transfection of miR-146a-5p inhibitor resulted in the opposite effects. Transfection of miR-146a-5p mimic/agomir inhibited the levels of interleukin-1 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB subunit p65. Dual luciferase reporter gene assay confirmed that miR-146a-5p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF-κB by SN50 in cultured microglia reversed the miR-146a-5p inhibitor-induced changes of inflammatory cytokines. In COH retinas, overexpression of miR-146a-5p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR-146a-5p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1/TRAF6/NF-κB signaling pathway in microglia.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"2115-2141"},"PeriodicalIF":5.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747034","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":"Cover Image, Volume 72, Issue 9","authors":"Paul F. Cullen,&nbsp;William J. Gammerdinger,&nbsp;Shannan J. Ho Sui,&nbsp;Arpan Guha Mazumder,&nbsp;Daniel Sun","doi":"10.1002/glia.24409","DOIUrl":"10.1002/glia.24409","url":null,"abstract":"<p>Cover Illustration: Confocal image of retinal astrocyte (green) isolated by microdissection from GFAP-Cre+ x Rpl22^HA/HA mouse showing HA-tagged ribosomes (red) present throughout the cell, including within endfeet processes, indicating that ribosome associated mRNA throughout the cell can be isolated by immunoprecipitation. The image also indicates how well astrocyte morphology are preserved in our microdissection method. Nuclei are labeled with DAPI in blue. (See Cullen, P., et al, https://doi.org/10.1002/glia.24571)\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 9","pages":"C1"},"PeriodicalIF":5.4,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141773279","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":"Myelin basic protein mRNA levels affect myelin sheath dimensions, architecture, plasticity, and density of resident glial cells","authors":"Hooman Bagheri,&nbsp;Hana Friedman,&nbsp;Amanda Hadwen,&nbsp;Celia Jarweh,&nbsp;Ellis Cooper,&nbsp;Lawrence Oprea,&nbsp;Claire Guerrier,&nbsp;Anmar Khadra,&nbsp;Armand Collin,&nbsp;Julien Cohen-Adad,&nbsp;Amanda Young,&nbsp;Gerardo Mendez Victoriano,&nbsp;Matthew Swire,&nbsp;Andrew Jarjour,&nbsp;Marie E. Bechler,&nbsp;Rachel S. Pryce,&nbsp;Pierre Chaurand,&nbsp;Lise Cougnaud,&nbsp;Dajana Vuckovic,&nbsp;Elliott Wilion,&nbsp;Owen Greene,&nbsp;Akiko Nishiyama,&nbsp;Anouk Benmamar-Badel,&nbsp;Trevor Owens,&nbsp;Vladimir Grouza,&nbsp;Marius Tuznik,&nbsp;Hanwen Liu,&nbsp;David A. Rudko,&nbsp;Jinyi Zhang,&nbsp;Katherine A. Siminovitch,&nbsp;Alan C. Peterson","doi":"10.1002/glia.24589","DOIUrl":"10.1002/glia.24589","url":null,"abstract":"<p>Myelin Basic Protein (MBP) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyelination. How different <i>Mbp</i> mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer-edited mouse lines that accumulate <i>Mbp</i> mRNA levels ranging from 8% to 160% of wild type. In young mice, reduced <i>Mbp</i> mRNA levels resulted in corresponding decreases in <i>Mbp</i> protein accumulation and myelin sheath thickness, confirming the previously demonstrated rate-limiting role of <i>Mbp</i> transcription in the control of initial myelin synthesis. However, despite maintaining lower line specific <i>Mbp</i> mRNA levels into old age, both MBP protein levels and myelin thickness improved or fully normalized at rates defined by the relative <i>Mbp</i> mRNA level. Sheath length, in contrast, was affected only when mRNA levels were very low, demonstrating that sheath thickness and length are not equally coupled to <i>Mbp</i> mRNA level. Striking abnormalities in sheath structure also emerged with reduced mRNA levels. Unexpectedly, an increase in the density of all glial cell types arose in response to reduced <i>Mbp</i> mRNA levels. This investigation extends understanding of the role MBP plays in myelin sheath elaboration, architecture, and plasticity across the mouse lifespan and illuminates a novel axis of glial cell crosstalk.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 10","pages":"1893-1914"},"PeriodicalIF":5.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632144","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":"Structural and molecular characterization of astrocyte and vasculature connectivity in the mouse hippocampus and cortex","authors":"Charlotte Lorin,&nbsp;Romain Guiet,&nbsp;Nicolas Chiaruttini,&nbsp;Giovanna Ambrosini,&nbsp;Elvis Boci,&nbsp;Marwan Abdellah,&nbsp;Henry Markram,&nbsp;Daniel Keller","doi":"10.1002/glia.24594","DOIUrl":"10.1002/glia.24594","url":null,"abstract":"<p>The relation of astrocytic endfeet to the vasculature plays a key functional role in the neuro-glia-vasculature unit. We characterize the spatial organization of astrocytes and the structural aspects that facilitate their involvement in molecular exchanges. Using double transgenic mice, we performed co-immunostaining, confocal microscopy, and three-dimensional digital segmentation to investigate the biophysical and molecular organization of astrocytes and their intricate endfoot network at the micrometer level in the isocortex and hippocampus. The results showed that hippocampal astrocytes had smaller territories, reduced endfoot dimensions, and fewer contacts with blood vessels compared with those in the isocortex. Additionally, we found that both connexins 43 and 30 have a higher density in the endfoot and the former is overexpressed relative to the latter. However, due to the limitations of the method, further studies are needed to determine the exact localization on the endfoot. The quantitative information obtained in this study will be useful for modeling the interactions of astrocytes with the vasculature.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"72 11","pages":"2001-2021"},"PeriodicalIF":5.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24594","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615410","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}