This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Neniskyte U, Gross CT. Errant gardeners: glial-cell-dependent synaptic pruning and neurodevelopmental disorders. Nat Rev Neurosci 2017, 18: 658–670.
Galloway DA, Phillips AEM, Owen DRJ, Moore CS. Phagocytosis in the Brain: Homeostasis and Disease. Front Immunol 2019, 10: 790.
Stephan AH, Barres BA, Stevens B. The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci 2012, 35: 369–389.
Magnus T, Chan A, Linker RA, Toyka KV, Gold R. Astrocytes are less efficient in the removal of apoptotic lymphocytes than microglia cells: implications for the role of glial cells in the inflamed central nervous system. J Neuropathol Exp Neurol 2002, 61: 760–766.
Chung WS, Clarke LE, Wang GX, Stafford BK, Sher A, Chakraborty C. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 2013, 504: 394–400.
Iram T, Ramirez-Ortiz Z, Byrne MH, Coleman UA, Kingery ND, Means TK, et al. Megf10 is a receptor for C1Q that mediates clearance of apoptotic cells by astrocytes. J Neurosci 2016, 36: 5185–5192.
Jung YJ, Chung WS. Phagocytic roles of glial cells in healthy and diseased brains. Biomol Ther (Seoul) 2018, 26: 350–357.
Damisah EC, Hill RA, Rai A, Chen F, Rothlin CV, Ghosh S, et al. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Sci Adv 2020, 6: eaba3239.
Chung WS, Allen NJ, Eroglu C. Astrocytes control synapse formation, function, and elimination. Cold Spring Harb Perspect Biol 2015, 7: a020370.
Zhang Y, Sloan SA, Clarke LE, Caneda C, Plaza CA, Blumenthal PD, et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 2016, 89: 37–53.
Sloan SA, Darmanis S, Huber N, Khan TA, Birey F, Caneda C, et al. Human astrocyte maturation captured in 3d cerebral cortical spheroids derived from pluripotent stem cells. Neuron 2017, 95(779–790): e776.
Lee JH, Kim JY, Noh S, Lee H, Lee SY, Mun JY, et al. Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis. Nature 2020.
Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, et al. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 2003, 9: 453–457.
Chung WS, Verghese PB, Chakraborty C, Joung J, Hyman BT, Ulrich JD, et al. Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes. Proc Natl Acad Sci U S A 2016, 113: 10186–10191.
Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 2016, 352: 712–716.
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017, 541: 481–487.
Qin C, Zhou LQ, Ma XT, Hu ZW, Yang S, Chen M, et al. Dual functions of microglia in ischemic stroke. Neurosci Bull 2019, 35: 921–933.
Vilalta A, Brown GC. Neurophagy, the phagocytosis of live neurons and synapses by glia, contributes to brain development and disease. FEBS J 2018, 285: 3566–3575.
Vasek MJ, Garber C, Dorsey D, Durrant DM, Bollman B, Soung A, et al. A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature 2016, 534: 538–543.
Tremblay ME, Marker DF, Puccini JM, Muly EC, Lu SM, Gelbard HA. Ultrastructure of microglia-synapse interactions in the HIV-1 Tat-injected murine central nervous system. Commun Integr Biol 2013, 6: e27670.
Shi Q, Colodner KJ, Matousek SB, Merry K, Hong S, Kenison JE, et al. Complement C3-deficient mice fail to display age-related hippocampal decline. J Neurosci 2015, 35: 13029–13042.
Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, et al. Schizophrenia risk from complex variation of complement component 4. Nature 2016, 530: 177–183.
Singh SK, Stogsdill JA, Pulimood NS, Dingsdale H, Kim YH, Pilaz LJ, et al. Astrocytes assemble thalamocortical synapses by bridging NRX1alpha and NL1 via hevin. Cell 2016, 164: 183–196.
Lehrman EK, Wilton DK, Litvina EY, Welsh CA, Chang ST, Frouin A, et al. CD47 protects synapses from excess microglia-mediated pruning during development. Neuron 2018, 100(120–134): e126.
Prada I, Gabrielli M, Turola E, Iorio A, D’Arrigo G, Parolisi R, et al. Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations. Acta Neuropathol 2018, 135: 529–550.
This Research Highlight was supported by Grants from the National Natural Science Foundation of China (31830033 and 82090032), the Program for Changjiang Scholars and Innovative Research Teams in University (IRT_16R37), and the Key-Area Research and Development Program of Guangdong Province, China (2018B030334001).
Conflict of interest
The authors declare that they have no competing interests.
About this article
Cite this article
Luo, T., Gao, TM. A Novel Phagocytic Role of Astrocytes in Activity-dependent Elimination of Mature Excitatory Synapses. Neurosci. Bull. 37, 1256–1259 (2021). https://doi.org/10.1007/s12264-021-00690-z