Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration
Summary: During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, understanding the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here, we...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-04-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225004626 |
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| author | Alfred Yu Camille Fang Li Xuan Tan Aparna Lakkaraju Luca Della Santina Yvonne Ou |
| author_facet | Alfred Yu Camille Fang Li Xuan Tan Aparna Lakkaraju Luca Della Santina Yvonne Ou |
| author_sort | Alfred Yu |
| collection | DOAJ |
| description | Summary: During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, understanding the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here, we analyzed microglia-mediated synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to hyper-ramified morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially protects ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting that microgliosis is the primary mechanism for increased synapse colocalization early after neuronal injury. |
| format | Article |
| id | doaj-art-60ecbedbba8b45c19de17c7ec936ae10 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-60ecbedbba8b45c19de17c7ec936ae102025-08-20T02:40:40ZengElsevieriScience2589-00422025-04-0128411220110.1016/j.isci.2025.112201Microglia target synaptic sites early during excitatory circuit disassembly in neurodegenerationAlfred Yu0Camille Fang1Li Xuan Tan2Aparna Lakkaraju3Luca Della Santina4Yvonne Ou5Department of Ophthalmology, UCSF School of Medicine, San Francisco, CA, USADepartment of Ophthalmology, UCSF School of Medicine, San Francisco, CA, USADepartment of Ophthalmology, UCSF School of Medicine, San Francisco, CA, USA; School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, Shandong, ChinaDepartment of Ophthalmology, UCSF School of Medicine, San Francisco, CA, USADepartment of Ophthalmology, UCSF School of Medicine, San Francisco, CA, USA; College of Optometry, University of Houston, Houston, TX, USADepartment of Ophthalmology, UCSF School of Medicine, San Francisco, CA, USA; Corresponding authorSummary: During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, understanding the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here, we analyzed microglia-mediated synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to hyper-ramified morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially protects ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting that microgliosis is the primary mechanism for increased synapse colocalization early after neuronal injury.http://www.sciencedirect.com/science/article/pii/S2589004225004626natural sciencesbiological sciencesneurosciencecellular neuroscience |
| spellingShingle | Alfred Yu Camille Fang Li Xuan Tan Aparna Lakkaraju Luca Della Santina Yvonne Ou Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration iScience natural sciences biological sciences neuroscience cellular neuroscience |
| title | Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration |
| title_full | Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration |
| title_fullStr | Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration |
| title_full_unstemmed | Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration |
| title_short | Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration |
| title_sort | microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration |
| topic | natural sciences biological sciences neuroscience cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225004626 |
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