Role of glia and extracellular matrix in controlling neuroplasticity in the central nervous system

Springer Science and Business Media LLC - Tập 45 - Trang 377-387 - 2023
Egor Dzyubenko1, Dirk M. Hermann1
1Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Essen, Germany

Tóm tắt

Neuronal plasticity is critical for the maintenance and modulation of brain activity. Emerging evidence indicates that glial cells actively shape neuroplasticity, allowing for highly flexible regulation of synaptic transmission, neuronal excitability, and network synchronization. Astrocytes regulate synaptogenesis, stabilize synaptic connectivity, and preserve the balance between excitation and inhibition in neuronal networks. Microglia, the brain-resident immune cells, continuously monitor and sculpt synapses, allowing for the remodeling of brain circuits. Glia-mediated neuroplasticity is driven by neuronal activity, controlled by a plethora of feedback signaling mechanisms and crucially involves extracellular matrix remodeling in the central nervous system. This review summarizes the key findings considering neurotransmission regulation and metabolic support by astrocyte-neuronal networks, and synaptic remodeling mediated by microglia. Novel data indicate that astrocytes and microglia are pivotal for controlling brain function, indicating the necessity to rethink neurocentric neuroplasticity views.

Tài liệu tham khảo

Fawcett JW (2015) The extracellular matrix in plasticity and regeneration after CNS injury and neurodegenerative disease. Prog Brain Res 218:213–226 Rusznak Z, Henskens W, Schofield E, Kim WS, Fu Y (2016) Adult neurogenesis and gliogenesis: possible mechanisms for neurorestoration. Exp Neurobiol 25(3):103–112 Domingues HS, Portugal CC, Socodato R, Relvas JB (2016) Oligodendrocyte, astrocyte, and microglia crosstalk in myelin development, damage, and repair. Front Cell Dev Biol 4:71 Dimou L, Gallo V (2015) NG2-glia and their functions in the central nervous system. Glia 63(8):1429–1451 Bergles DE, Richardson WD (2015) Oligodendrocyte development and plasticity. Cold Spring Harb Perspect Biol 8(2):a020453 Dzyubenko E, Gottschling C, Faissner A (2016) Neuron-glia interactions in neural plasticity: contributions of neural extracellular matrix and perineuronal nets. Neural Plast 2016:5214961 Nicholson C, Hrabětová S (2017) Brain extracellular space: the final frontier of neuroscience. Biophys J 113(10):2133–2142 Arranz AM, Perkins KL, Irie F, Lewis DP, Hrabe J, Xiao F, Itano N, Kimata K, Hrabetova S, Yamaguchi Y (2014) Hyaluronan deficiency due to Has3 knock-out causes altered neuronal activity and seizures via reduction in brain extracellular space. J Neurosci 34(18):6164–6176 Fawcett JW, Oohashi T, Pizzorusso T (2019) The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function. Nat Rev Neurosci 20(8):451–465 Frischknecht R, Seidenbecher CI (2008) The crosstalk of hyaluronan-based extracellular matrix and synapses. Neuron Glia Biol 4(3):249–257 Hubbard JA, Binder DK (2016) History of Astrocytes. In: Hubbard JA, Binder DK (eds) Astrocytes and epilepsy. Academic Press, San Diego, pp 1–38 Lanjakornsiripan D, Pior BJ, Kawaguchi D, Furutachi S, Tahara T, Katsuyama Y, Suzuki Y, Fukazawa Y, Gotoh Y (2018) Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers. Nat Commun 9(1):1623 Gavrilov N, Golyagina I, Brazhe A, Scimemi A, Turlapov V, Semyanov A (2018) Astrocytic coverage of dendritic spines, dendritic shafts, and axonal boutons in hippocampal neuropil. Front Cell Neurosci 12:248 Arizono M, Inavalli V, Panatier A, Pfeiffer T, Angibaud J, Levet F, Ter Veer MJT, Stobart J, Bellocchio L, Mikoshiba K, Marsicano G, Weber B, Oliet SHR, Nagerl UV (2020) Structural basis of astrocytic Ca(2+) signals at tripartite synapses. Nat Commun 11(1):1906 Verkhratsky A, Nedergaard M (2014) Astroglial cradle in the life of the synapse. Philos Trans R Soc Lond B Biol Sci 369(1654):20130595 Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32(8):421–431 Dalva MB, McClelland AC, Kayser MS (2007) Cell adhesion molecules: signalling functions at the synapse. Nat Rev Neurosci 8(3):206–220 Allen NJ, Bennett ML, Foo LC, Wang GX, Chakraborty C, Smith SJ, Barres BA (2012) Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature 486(7403):410–414 Hillen AEJ, Burbach JPH, Hol EM (2018) Cell adhesion and matricellular support by astrocytes of the tripartite synapse. Prog Neurobiol 165-167:66–86 Fornasiero EF, Mandad S, Wildhagen H, Alevra M, Rammner B, Keihani S, Opazo F, Urban I, Ischebeck T, Sakib MS, Fard MK, Kirli K, Centeno TP, Vidal RO, Rahman RU, Benito E, Fischer A, Dennerlein S, Rehling P et al (2018) Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions. Nat Commun 9(1):4230 Dankovich TM, Rizzoli SO (2022) The synaptic extracellular matrix: long-lived, stable, and still remarkably dynamic. Front Synaptic Neurosci 14:854956 Dityatev A, Schachner M, Sonderegger P (2010) The dual role of the extracellular matrix in synaptic plasticity and homeostasis. Nat Rev Neurosci 11(11):735–746 Dityatev A, Rusakov DA (2011) Molecular signals of plasticity at the tetrapartite synapse. Curr Opin Neurobiol 21(2):353–359 Sykova E (2001) Glial diffusion barriers during aging and pathological states. Prog Brain Res 132:339–363 Murphy-Royal C, Dupuis JP, Varela JA, Panatier A, Pinson B, Baufreton J, Groc L, Oliet SH (2015) Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission. Nat Neurosci 18(2):219–226 Benediktsson AM, Marrs GS, Tu JC, Worley PF, Rothstein JD, Bergles DE, Dailey ME (2012) Neuronal activity regulates glutamate transporter dynamics in developing astrocytes. Glia 60(2):175–188 Poitry-Yamate CL, Vutskits L, Rauen T (2002) Neuronal-induced and glutamate-dependent activation of glial glutamate transporter function. J Neurochem 82(4):987–997 Ashpole NM, Chawla AR, Martin MP, Brustovetsky T, Brustovetsky N, Hudmon A (2013) Loss of calcium/calmodulin-dependent protein kinase II activity in cortical astrocytes decreases glutamate uptake and induces neurotoxic release of ATP *. J Biol Chem 288(20):14599–14611 Underhill SM, Wheeler DS, Amara SG (2015) Differential regulation of two isoforms of the glial glutamate transporter EAAT2 by DLG1 and CaMKII. J Neurosci 35(13):5260–5270 Sakers K, Lake AM, Khazanchi R, Ouwenga R, Vasek MJ, Dani A, Dougherty JD (2017) Astrocytes locally translate transcripts in their peripheral processes. Proc Natl Acad Sci U S A 114(19):E3830–E3838 Boivin JR, Nedivi E (2018) Functional implications of inhibitory synapse placement on signal processing in pyramidal neuron dendrites. Curr Opin Neurobiol 51:16–22 Minelli A, DeBiasi S, Brecha NC, Zuccarello LV, Conti F (1996) GAT-3, a high-affinity GABA plasma membrane transporter, is localized to astrocytic processes, and it is not confined to the vicinity of GABAergic synapses in the cerebral cortex. J Neurosci 16(19):6255–6264 Araque A, Carmignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A (2014) Gliotransmitters travel in time and space. Neuron 81(4):728–739 Porter JT, McCarthy KD (1997) Astrocytic neurotransmitter receptors in situ and in vivo. Prog Neurobiol 51(4):439–455 Covelo A, Araque A (2018) Neuronal activity determines distinct gliotransmitter release from a single astrocyte. Elife 7:e32237. https://doi.org/10.7554/eLife.32237 Schipke CG, Haas B, Kettenmann H (2008) Astrocytes discriminate and selectively respond to the activity of a subpopulation of neurons within the barrel cortex. Cereb Cortex 18(10):2450–2459 Dzyubenko E, Prazuch W, Pillath-Eilers M, Polanska J, Hermann DM (2021) Analysing intercellular communication in astrocytic networks using “astral”. Front Cell Neurosci 15:689268 Wang Y, DelRosso NV, Vaidyanathan TV, Cahill MK, Reitman ME, Pittolo S, Mi X, Yu G, Poskanzer KE (2019) Accurate quantification of astrocyte and neurotransmitter fluorescence dynamics for single-cell and population-level physiology. Nat Neurosci 22(11):1936–1944 Rungta RL, Bernier L-P, Dissing-Olesen L, Groten CJ, LeDue JM, Ko R, Drissler S, MacVicar BA (2016) Ca2+ transients in astrocyte fine processes occur via Ca2+ influx in the adult mouse hippocampus. Glia 64(12):2093–2103 Verkhratsky A, Rodriguez JJ, Parpura V (2012) Calcium signalling in astroglia. Mol Cell Endocrinol 353(1-2):45–56 Duffy S, MacVicar BA (1995) Adrenergic calcium signaling in astrocyte networks within the hippocampal slice. J Neurosci 15(8):5535–5550 Nedergaard M (1994) Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. Science 263(5154):1768–1771 Boddum K, Jensen TP, Magloire V, Kristiansen U, Rusakov DA, Pavlov I, Walker MC (2016) Astrocytic GABA transporter activity modulates excitatory neurotransmission. Nat Commun 7:13572 Perea G, Yang A, Boyden ES, Sur M (2014) Optogenetic astrocyte activation modulates response selectivity of visual cortex neurons in vivo. Nat Commun 5(1):3262 Poskanzer KE, Yuste R (2016) Astrocytes regulate cortical state switching in vivo. Proc Natl Acad Sci U S A 113(19):E2675–E2684 Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6(8):626–640 Malarkey EB, Parpura V (2008)Mechanisms of glutamate release from astrocytes. Neurochem Int 52(1-2):142-54 Perea G, Araque A (2007) Astrocytes potentiate transmitter release at single hippocampal synapses. Science 317(5841):1083–1086 Neame S, Safory H, Radzishevsky I, Touitou A, Marchesani F, Marchetti M, Kellner S, Berlin S, Foltyn VN, Engelender S, Billard JM, Wolosker H (2019) The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. Proc Natl Acad Sci U S A 116(41):20736–20742 Yang Y, Ge W, Chen Y, Zhang Z, Shen W, Wu C, Poo M, Duan S (2003) Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proc Natl Acad Sci U S A 100(25):15194–15199 Deemyad T, Luthi J, Spruston N (2018) Astrocytes integrate and drive action potential firing in inhibitory subnetworks. Nat Commun 9(1):4336 Zhang JM, Wang HK, Ye CQ, Ge W, Chen Y, Jiang ZL, Wu CP, Poo MM, Duan S (2003) ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron 40(5):971–982 Mariotti L, Losi G, Sessolo M, Marcon I, Carmignoto G (2016) The inhibitory neurotransmitter GABA evokes long-lasting Ca(2+) oscillations in cortical astrocytes. Glia 64(3):363–373 Perea G, Gomez R, Mederos S, Covelo A, Ballesteros JJ, Schlosser L, Hernandez-Vivanco A, Martin-Fernandez M, Quintana R, Rayan A, Diez A, Fuenzalida M, Agarwal A, Bergles DE, Bettler B, Manahan-Vaughan D, Martin ED, Kirchhoff F, Araque A (2016) Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks. Elife 5:e20362. https://doi.org/10.7554/eLife.20362 Matos M, Bosson A, Riebe I, Reynell C, Vallee J, Laplante I, Panatier A, Robitaille R, Lacaille JC (2018) Astrocytes detect and upregulate transmission at inhibitory synapses of somatostatin interneurons onto pyramidal cells. Nat Commun 9(1):4254 Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43(5):729–743 Mederos S, Perea G (2019) GABAergic-astrocyte signaling: a refinement of inhibitory brain networks. Glia 67(10):1842–1851 Doron A, Rubin A, Benmelech-Chovav A, Benaim N, Carmi T, Refaeli R, Novick N, Kreisel T, Ziv Y, Goshen I (2022) Hippocampal astrocytes encode reward location. Nature 609(7928):772–778 Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG (2007) Synaptic islands defined by the territory of a single astrocyte. J Neurosci 27(24):6473–6477 Anders S, Minge D, Griemsmann S, Herde MK, Steinhauser C, Henneberger C (2014) Spatial properties of astrocyte gap junction coupling in the rat hippocampus. Philos Trans R Soc Lond B Biol Sci 369(1654):20130600 Bedner P, Dupper A, Huttmann K, Muller J, Herde MK, Dublin P, Deshpande T, Schramm J, Haussler U, Haas CA, Henneberger C, Theis M, Steinhauser C (2015) Astrocyte uncoupling as a cause of human temporal lobe epilepsy. Brain 138(Pt 5):1208–1222 Rouach N, Koulakoff A, Abudara V, Willecke K, Giaume C (2008) Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322(5907):1551–1555 Pandit S, Neupane C, Woo J, Sharma R, Nam MH, Lee GS, Yi MH, Shin N, Kim DW, Cho H, Jeon BH, Kim HW, Lee CJ, Park JB (2020) Bestrophin1-mediated tonic GABA release from reactive astrocytes prevents the development of seizure-prone network in kainate-injected hippocampi. Glia 68(5):1065–1080 Woo J, Min JO, Kang DS, Kim YS, Jung GH, Park HJ, Kim S, An H, Kwon J, Kim J, Shim I, Kim HG, Lee CJ, Yoon BE (2018) Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum. Proc Natl Acad Sci U S A 115(19):5004–5009 Egawa K, Yamada J, Furukawa T, Yanagawa Y, Fukuda A (2013) Cl(-) homeodynamics in gap junction-coupled astrocytic networks on activation of GABAergic synapses. J Physiol 591(16):3901–3917 Olsen ML, Sontheimer H (2008) Functional implications for Kir4.1 channels in glial biology: from K+ buffering to cell differentiation. J Neurochem 107(3):589–601 Larsen BR, Stoica A, MacAulay N (2016) Managing brain extracellular K(+) during neuronal activity: the physiological role of the Na(+)/K(+)-ATPase subunit isoforms. Front Physiol 7:141 Bruckner G, Brauer K, Hartig W, Wolff JR, Rickmann MJ, Derouiche A, Delpech B, Girard N, Oertel WH, Reichenbach A (1993) Perineuronal nets provide a polyanionic, glia-associated form of microenvironment around certain neurons in many parts of the rat brain. Glia 8(3):183–200 Dityatev A, Bruckner G, Dityateva G, Grosche J, Kleene R, Schachner M (2007) Activity-dependent formation and functions of chondroitin sulfate-rich extracellular matrix of perineuronal nets. Dev Neurobiol 67(5):570–588 Bauernfeind AL, Barks SK, Duka T, Grossman LI, Hof PR, Sherwood CC (2014) Aerobic glycolysis in the primate brain: reconsidering the implications for growth and maintenance. Brain Struct Funct 219(4):1149–1167 Lunt SY, Vander Heiden MG (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27:441–464 Belanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14(6):724–738 Yang J, Ruchti E, Petit JM, Jourdain P, Grenningloh G, Allaman I, Magistretti PJ (2014) Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc Natl Acad Sci U S A 111(33):12228–12233 Choi Y, Chen HV, Lipton SA (2001) Three pairs of cysteine residues mediate both redox and zn2+ modulation of the nmda receptor. J Neurosci 21(2):392–400 Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144(5):810–823 Anlauf E, Derouiche A (2013) Glutamine synthetase as an astrocytic marker: its cell type and vesicle localization. Front Endocrinol (Lausanne) 4:144 Leke R, Schousboe A (2016) The glutamine transporters and their role in the glutamate/GABA-glutamine cycle. Adv Neurobiol 13:223–257 Hagglund MG, Sreedharan S, Nilsson VC, Shaik JH, Almkvist IM, Backlin S, Wrange O, Fredriksson R (2011) Identification of SLC38A7 (SNAT7) protein as a glutamine transporter expressed in neurons. J Biol Chem 286(23):20500–20511 Schousboe A, Scafidi S, Bak LK, Waagepetersen HS, McKenna MC (2014) Glutamate metabolism in the brain focusing on astrocytes. Adv Neurobiol 11:13–30 Andersen JV, Jakobsen E, Westi EW, Lie MEK, Voss CM, Aldana BI, Schousboe A, Wellendorph P, Bak LK, Pinborg LH, Waagepetersen HS (2020) Extensive astrocyte metabolism of gamma-aminobutyric acid (GABA) sustains glutamine synthesis in the mammalian cerebral cortex. Glia 68(12):2601–2612 Sonnewald U, Westergaard N, Schousboe A, Svendsen JS, Unsgard G, Petersen SB (1993) Direct demonstration by [13C]NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons. Neurochem Int 22(1):19–29 Schousboe A, Bak LK, Waagepetersen HS (2013) Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA. Front Endocrinol (Lausanne) 4:102 Qureshi T, Sorensen C, Berghuis P, Jensen V, Dobszay MB, Farkas T, Dalen KT, Guo C, Hassel B, Utheim TP, Hvalby O, Hafting T, Harkany T, Fyhn M, Chaudhry FA (2019) The glutamine transporter Slc38a1 regulates GABAergic neurotransmission and synaptic plasticity. Cereb Cortex 29(12):5166–5179 Ivens S, Caliskan G, Papageorgiou I, Cesetti T, Malich A, Kann O, Heinemann U, Stork O, Albrecht A (2019) Persistent increase in ventral hippocampal long-term potentiation by juvenile stress: a role for astrocytic glutamine synthetase. Glia 67(12):2279–2293 Hensch TK (2005) Critical period plasticity in local cortical circuits. Nat Rev Neurosci 6(11):877–888 Takesian AE, Hensch TK (2013) Balancing plasticity/stability across brain development. Prog Brain Res 207:3–34 Gundelfinger ED, Frischknecht R, Choquet D, Heine M (2010) Converting juvenile into adult plasticity: a role for the brain’s extracellular matrix. Eur J Neurosci 31(12):2156–2165 Carulli D, Foscarin S, Faralli A, Pajaj E, Rossi F (2013) Modulation of semaphorin3A in perineuronal nets during structural plasticity in the adult cerebellum. Mol Cell Neurosci 57:10–22 Pearson CS, Mencio CP, Barber AC, Martin KR, Geller HM (2018) Identification of a critical sulfation in chondroitin that inhibits axonal regeneration. Elife 7:e37139. https://doi.org/10.7554/eLife.37139 Dzyubenko E, Fleischer M, Manrique-Castano D, Borbor M, Kleinschnitz C, Faissner A, Hermann DM (2021) Inhibitory control in neuronal networks relies on the extracellular matrix integrity. Cell Mol Life Sci 78(14):5647–5663 Huntley GW (2012) Synaptic circuit remodelling by matrix metalloproteinases in health and disease. Nat Rev Neurosci 13(11):743–757 Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74(4):691–705 Weinhard L, di Bartolomei G, Bolasco G, Machado P, Schieber NL, Neniskyte U, Exiga M, Vadisiute A, Raggioli A, Schertel A, Schwab Y, Gross CT (2018) Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction. Nat Commun 9(1):1228 Bennett ML, Bennett FC (2020) The influence of environment and origin on brain resident macrophages and implications for therapy. Nat Neurosci 23(2):157–166 Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314–1318 Szalay G, Martinecz B, Lenart N, Kornyei Z, Orsolits B, Judak L, Csaszar E, Fekete R, West BL, Katona G, Rozsa B, Denes A (2016) Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke. Nat Commun 7:11499 Cserep C, Posfai B, Lenart N, Fekete R, Laszlo ZI, Lele Z, Orsolits B, Molnar G, Heindl S, Schwarcz AD, Ujvari K, Kornyei Z, Toth K, Szabadits E, Sperlagh B, Baranyi M, Csiba L, Hortobagyi T, Magloczky Z et al (2020) Microglia monitor and protect neuronal function through specialized somatic purinergic junctions. Science 367(6477):528–537 Liu YU, Ying Y, Li Y, Eyo UB, Chen T, Zheng J, Umpierre AD, Zhu J, Bosco DB, Dong H, Wu LJ (2019) Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nat Neurosci 22(11):1771–1781 Logiacco F, Xia P, Georgiev SV, Franconi C, Chang YJ, Ugursu B, Sporbert A, Kuhn R, Kettenmann H, Semtner M (2021) Microglia sense neuronal activity via GABA in the early postnatal hippocampus. Cell Rep 37(13):110128 Umpierre AD, Bystrom LL, Ying Y, Liu YU, Worrell G, Wu LJ (2020) Microglial calcium signaling is attuned to neuronal activity in awake mice. Elife 7:9:e56502. https://doi.org/10.7554/eLife.56502 Nguyen PT, Dorman LC, Pan S, Vainchtein ID, Han RT, Nakao-Inoue H, Taloma SE, Barron JJ, Molofsky AB, Kheirbek MA, Molofsky AV (2020) Microglial remodeling of the extracellular matrix promotes synapse plasticity. Cell 182(2):388–403.e15 Favuzzi E, Huang S, Saldi GA, Binan L, Ibrahim LA, Fernandez-Otero M, Cao Y, Zeine A, Sefah A, Zheng K, Xu Q, Khlestova E, Farhi SL, Bonneau R, Datta SR, Stevens B, Fishell G (2021) GABA-receptive microglia selectively sculpt developing inhibitory circuits. Cell 184(15):4048–4063 e32 Kovacs RA, Vadaszi H, Bulyaki E, Torok G, Toth V, Matyas D, Kun J, Hunyadi-Gulyas E, Fedor FZ, Csincsi A, Medzihradszky K, Homolya L, Juhasz G, Kekesi KA, Jozsi M, Gyorffy BA, Kardos J (2020) Identification of neuronal pentraxins as synaptic binding partners of C1q and the involvement of NP1 in synaptic pruning in adult mice. Front Immunol 11:599771 Scott-Hewitt N, Perrucci F, Morini R, Erreni M, Mahoney M, Witkowska A, Carey A, Faggiani E, Schuetz LT, Mason S, Tamborini M, Bizzotto M, Passoni L, Filipello F, Jahn R, Stevens B, Matteoli M (2020) Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia. EMBO J 39(16):e105380 Vainchtein ID, Chin G, Cho FS, Kelley KW, Miller JG, Chien EC, Liddelow SA, Nguyen PT, Nakao-Inoue H, Dorman LC, Akil O, Joshita S, Barres BA, Paz JT, Molofsky AB, Molofsky AV (2018) Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development. Science 359(6381):1269–1273 Dou Y, Wu H-J, Li H-Q, Qin S, Wang Y-E, Li J, Lou H-F, Chen Z, Li X-M, Luo Q-M, Duan S (2012) Microglial migration mediated by ATP-induced ATP release from lysosomes. Cell Res 22(6):1022–1033 Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan W-B, Julius D (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9(12):1512–1519 Harrison JK, Jiang Y, Chen S, Xia Y, Maciejewski D, McNamara RK, Streit WJ, Salafranca MN, Adhikari S, Thompson DA (1998) Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci 95(18):10896–10901 Hughes PM, Botham MS, Frentzel S, Mir A, Perry VH (2002) Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS. Glia 37(4):314–327 Eyo UB, Wu LJ (2019) Microglia: lifelong patrolling immune cells of the brain. Prog Neurobiol 179:101614 Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333(6048):1456–1458 Dejanovic B, Huntley MA, De Mazière A, Meilandt WJ, Wu T, Srinivasan K, Jiang Z, Gandham V, Friedman BA, Ngu H, Foreman O, Carano RAD, Chih B, Klumperman J, Bakalarski C, Hanson JE, Sheng M (2018) Changes in the synaptic proteome in tauopathy and rescue of tau-induced synapse loss by C1q antibodies. Neuron 100(6):1322–1336.e7 Cheadle L, Rivera SA, Phelps JS, Ennis KA, Stevens B, Burkly LC, Lee W-CA, Greenberg ME (2020) Sensory experience engages microglia to shape neural connectivity through a non-phagocytic mechanism. Neuron 108(3):451–468.e9 Allen NJ, Eroglu C (2017) Cell biology of astrocyte-synapse interactions. Neuron 96(3):697–708 Kucukdereli H, Allen NJ, Lee AT, Feng A, Ozlu MI, Conatser LM, Chakraborty C, Workman G, Weaver M, Sage EH, Barres BA, Eroglu C (2011) Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC. Proc Natl Acad Sci U S A 108(32):E440–E449 Dzyubenko E, Manrique-Castano D, Kleinschnitz C, Faissner A, Hermann DM (2018) Role of immune responses for extracellular matrix remodeling in the ischemic brain. Ther Adv Neurol Disord 11:1756286418818092 Enzmann G, Mysiorek C, Gorina R, Cheng YJ, Ghavampour S, Hannocks MJ, Prinz V, Dirnagl U, Endres M, Prinz M, Beschorner R, Harter PN, Mittelbronn M, Engelhardt B, Sorokin L (2013) The neurovascular unit as a selective barrier to polymorphonuclear granulocyte (PMN) infiltration into the brain after ischemic injury. Acta Neuropathol 125(3):395–412 Neumann J, Riek-Burchardt M, Herz J, Doeppner TR, Konig R, Hutten H, Etemire E, Mann L, Klingberg A, Fischer T, Gortler MW, Heinze HJ, Reichardt P, Schraven B, Hermann DM, Reymann KG, Gunzer M (2015) Very-late-antigen-4 (VLA-4)-mediated brain invasion by neutrophils leads to interactions with microglia, increased ischemic injury and impaired behavior in experimental stroke. Acta Neuropathol 129(2):259–277 Malone K, Amu S, Moore AC, Waeber C (2019) Immunomodulatory therapeutic strategies in stroke. Front Pharmacol 10:630 Qiu J, Nishimura M, Wang Y, Sims JR, Qiu S, Savitz SI, Salomone S, Moskowitz MA (2008) Early release of HMGB-1 from neurons after the onset of brain ischemia. J Cereb Blood Flow Metab 28(5):927–938 Sun Y, Hei M, Fang Z, Tang Z, Wang B, Hu N (2019) High-mobility group box 1 contributes to cerebral cortex injury in a neonatal hypoxic-ischemic rat model by regulating the phenotypic polarization of microglia. Front Cell Neurosci 13:506 Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Munch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541(7638):481–487 M. Borbor, D. Yin, U. Brockmeier, C. Wang, M. Doeckel, M. Pillath-Eilers, B. Kaltwasser, D.M. Hermann, E. Dzyubenko, Neurotoxicity of ischemic astrocytes involves STAT3-mediated metabolic switching and depends on glycogen usage, Glia n/a(n/a) (2023). Al'Qteishat A, Gaffney J, Krupinski J, Rubio F, West D, Kumar S, Kumar P, Mitsios N, Slevin M (2006) Changes in hyaluronan production and metabolism following ischaemic stroke in man. Brain 129(Pt 8):2158–2176 Dzyubenko E, Manrique-Castano D, Pillath-Eilers M, Vasileiadou P, Reinhard J, Faissner A, Hermann DM (2022) Tenascin-C restricts reactive astrogliosis in the ischemic brain. Matrix Biol 110:1–15 Manrique-Castano D, Dzyubenko E, Borbor M, Vasileiadou P, Kleinschnitz C, Roll L, Faissner A, Hermann DM (2021) Tenascin-C preserves microglia surveillance and restricts leukocyte and, more specifically, T cell infiltration of the ischemic brain. Brain Behav Immun 91:639–648 Dzyubenko E, Manrique-Castano D, Kleinschnitz C, Faissner A, Hermann DM (2018) Topological remodeling of cortical perineuronal nets in focal cerebral ischemia and mild hypoperfusion. Matrix Biol 74:121–132 Hartig W, Mages B, Aleithe S, Nitzsche B, Altmann S, Barthel H, Krueger M, Michalski D (2017) Damaged neocortical perineuronal nets due to experimental focal cerebral ischemia in mice, rats and sheep. Front Integr Neurosci 11(15):15 Baik SH, Kang S, Lee W, Choi H, Chung S, Kim JI, Mook-Jung I (2019) A breakdown in metabolic reprogramming causes microglia dysfunction in Alzheimer’s disease. Cell Metab 30(3):493–507 e6 Lively S, Schlichter LC (2013) The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion. J Neuroinflammation 10:75 Crapser JD, Ochaba J, Soni N, Reidling JC, Thompson LM, Green KN (2020) Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington’s disease. Brain 143(1):266–288 Crapser JD, Spangenberg EE, Barahona RA, Arreola MA, Hohsfield LA, Green KN (2020) Microglia facilitate loss of perineuronal nets in the Alzheimer’s disease brain. EBioMedicine 58:102919 Rothhammer V, Borucki DM, Tjon EC, Takenaka MC, Chao CC, Ardura-Fabregat A, de Lima KA, Gutierrez-Vazquez C, Hewson P, Staszewski O, Blain M, Healy L, Neziraj T, Borio M, Wheeler M, Dragin LL, Laplaud DA, Antel J, Alvarez JI et al (2018) Microglial control of astrocytes in response to microbial metabolites. Nature 557(7707):724–728 Wheeler MA, Jaronen M, Covacu R, Zandee SEJ, Scalisi G, Rothhammer V, Tjon EC, Chao CC, Kenison JE, Blain M, Rao VTS, Hewson P, Barroso A, Gutierrez-Vazquez C, Prat A, Antel JP, Hauser R, Quintana FJ (2019) Environmental control of astrocyte pathogenic activities in CNS inflammation. Cell 176(3):581–596.e18 Silva RV, Biskup K, Zabala-Jouvin JK, Batzdorf CS, Stellmach C, Morr AS, Sack I, Ludwig A, Blanchard V, Infante-Duarte C (2023) Brain inflammation induces alterations in glycosaminoglycan metabolism and subsequent changes in CS-4S and hyaluronic acid. Int J Biol Macromol 230:123214