AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Stress and Brain Article
PDF (1.2 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Review Article | Open Access

The role of purinergic signaling in microglial responses

 Department of Neurobiology & Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
 NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain–Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China
Show Author Information

Graphical Abstract

Abstract

Microglia, the primary immune cells in the central nervous system (CNS), are key to the maintenance of homeostasis in the brain parenchyma. In the intact brain, microglia continuously survey the microenvironment with ramified processes. Upon disease and/or damage, they rapidly convert into an amoeboid morphology, move toward the injury, and release cytokines to repair damage or clear debris. Purinergic signaling plays an important role in regulating microglial dynamics and immune responses. Specific purinergic receptors have been shown to participate in different aspects of microglial responses in the normal and diseased brains. In this review, we focus on the role of purinergic signaling-mediated microglial responses under physiological and pathological conditions.

Keywords

microgliapurinergic signalingadenosine triphosphate (ATP)purinergic type 1 (P1) receptorspurinergic type 2 (P2) receptors

References

[1]
Butovsky, O., Weiner, H. L. Microglial signatures and their role in health and disease. Nature Reviews Neuroscience, 2018, 19(10): 622–635.
Crossref Google Scholar
[2]
Song, W. M., Colonna, M. The microglial response to neurodegenerative disease. In: Alt, F. (eds.), Advances in Immunology. Amsterdam: Elsevier, 2018: 1–50.
Crossref
[3]
Färber, K., Kettenmann, H. Purinergic signaling and microglia. Pflügers Archiv - European Journal of Physiology, 2006, 452(5): 615–621.
Crossref Google Scholar
[4]
Koizumi, S., Ohsawa, K., Inoue, K., Kohsaka, S. Purinergic receptors in microglia: Functional modal shifts of microglia mediated by P2 and P1 receptors. Glia, 2013, 61(1): 47–54.
Crossref Google Scholar
[5]
Calovi, S., Mut-Arbona, P., Sperlágh, B. Microglia and the purinergic signaling system. Neuroscience, 2019, 405: 137–147.
Crossref Google Scholar
[6]
Vainchtein, I. D., Molofsky, A. V. Astrocytes and microglia: In sickness and in health. Trends in Neurosciences, 2020, 43(3): 144–154.
Crossref Google Scholar
[7]
Burnstock, G. Overview: Purinergic mechanisms. Annals of the New York Academy of Sciences, 1990, 603(1): 1–17.
Crossref Google Scholar
[8]
von Kügelgen, I., Hoffmann, K. Pharmacology and structure of P2Y receptors. Neuropharmacology, 2016, 104: 50–61.
Crossref Google Scholar
[9]
Färber, K., Kettenmann, H. Physiology of microglial cells. Brain Research Reviews, 2005, 48(2): 133–143.
Crossref Google Scholar
[10]
Sasaki, Y., Hoshi, M., Akazawa, C., Nakamura, Y., Tsuzuki, H., Inoue, K., Kohsaka, S. Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain. Glia, 2003, 44(3): 242–250.
Crossref Google Scholar
[11]
Hickman, S. E., Kingery, N. D., Ohsumi, T. K., Borowsky, M. L., Wang, L. C., Means, T. K., El Khoury, J. The microglial sensome revealed by direct RNA sequencing. Nature Neuroscience, 2013, 16(12): 1896–1905.
Crossref Google Scholar
[12]
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Ben, D. K., Wu, P. M., Doykan, C. E. et al. Identification of a unique TGF-β–dependent molecular and functional signature in microglia. Nature Neuroscience, 2014, 17(1): 131–143.
Crossref Google Scholar
[13]
Haynes, S. E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M. E., Gan, W. B., Julius, D. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nature Neuroscience, 2006, 9(12): 1512–1519.
Crossref Google Scholar
[14]
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., Gan, W. B. ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience, 2005, 8(6): 752–758.
Crossref Google Scholar
[15]
Dissing-Olesen, L., LeDue, J. M., Rungta, R. L., Hefendehl, J. K., Choi, H. B., MacVicar, B. A. Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. Journal of Neuroscience, 2014, 34(32): 10511–10527.
Crossref Google Scholar
[16]
Eyo, U. B., Peng, J., Swiatkowski, P., Mukherjee, A., Bispo, A., Wu, L. J. Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after status epilepticus. Journal of Neuroscience, 2014, 34(32): 10528–10540.
Crossref Google Scholar
[17]
Irino, Y., Nakamura, Y., Inoue, K., Kohsaka, S., Ohsawa, K. Akt activation is involved in P2Y12 receptor-mediated chemotaxis of microglia. Journal of Neuroscience Research, 2008, 86(7): 1511–1519.
Crossref Google Scholar
[18]
Ohsawa, K., Irino, Y., Sanagi, T., Nakamura, Y., Suzuki, E., Inoue, K., Kohsaka, S. P2Y12 receptor-mediated integrin-β1 activation regulates microglial process extension induced by ATP. Glia, 2010, 58(7): 790–801.
Crossref Google Scholar
[19]
Madry, C., Kyrargyri, V., Arancibia-Cárcamo, I. L., Jolivet, R., Kohsaka, S., Bryan, R. M., Attwell, D. Microglial ramification, surveillance, and interleukin-1β release are regulated by the two-pore domain K+ channel THIK-1. Neuron, 2018, 97(2): 299–312.e6.
Crossref Google Scholar
[20]
Swiatkowski, P., Murugan, M., Eyo, U. B., Wang, Y., Rangaraju, S., Oh, S. B., Wu, L. J. Activation of microglial P2Y12 receptor is required for outward potassium currents in response to neuronal injury. Neuroscience, 2016, 318: 22–33.
Crossref Google Scholar
[21]
Stowell, R. D., Sipe, G. O., Dawes, R. P., Batchelor, H. N., Lordy, K. A., Whitelaw, B. S., Stoessel, M. B., Bidlack, J. M., Brown, E., Sur, M. et al. Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex. Nature Neuroscience, 2019, 22(11): 1782–1792.
Crossref Google Scholar
[22]
Liu, Y. U., Ying, Y. L., Li, Y. J., Eyo, U. B., Chen, T. J., Zheng, J. Y., Umpierre, A. D., Zhu, J., Bosco, D. B., Dong, H. L. et al. Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nature Neuroscience, 2019, 22(11): 1771–1781.
Crossref Google Scholar
[23]
Suzuki, T., Kohyama, K., Moriyama, K., Ozaki, M., Hasegawa, S., Ueno, T., Saitoe, M., Morio, T., Hayashi, M., Sakuma, H. Extracellular ADP augments microglial inflammasome and NF-κB activation via the P2Y12 receptor. European Journal of Immunology, 2020, 50(2): 205–219.
Crossref Google Scholar
[24]
Sipe, G. O., Lowery, R. L., Tremblay, M. È., Kelly, E. A., Lamantia, C. E., Majewska, A. K. Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex. Nature Communications, 2016, 7: 10905.
Crossref Google Scholar
[25]
Peng, J. Y., Liu, Y., Umpierre, A. D., Xie, M. L., Tian, D. S., Richardson, J. R., Wu, L. J. Microglial P2Y12 receptor regulates ventral hippocampal CA1 neuronal excitability and innate fear in mice. Molecular Brain, 2019, 12: 71.
Crossref Google Scholar
[26]
Cserép, C., Pósfai, B., Lénárt, N., Fekete, R., László, Z. I., Lele, Z., Orsolits, B., Molnár, G., Heindl, S., Schwarcz, A. D., et al. Microglia monitor and protect neuronal function through specialized somatic purinergic junctions. Science, 2020, 367(6477): 528–537.
Crossref Google Scholar
[27]
Maeda, M., Tsuda, M., Tozaki-Saitoh, H., Inoue, K., Kiyama, H. Nerve injury-activated microglia engulf myelinated axons in a P2Y12 signaling-dependent manner in the dorsal horn. Glia, 2010, 58(15): 1838–1846.
Crossref Google Scholar
[28]
Gu, N., Peng, J. Y., Murugan, M., Wang, X., Eyo, U. B., Sun, D. M., Ren, Y., Dicicco-Bloom, E., Young, W., Dong, H. L. et al. Spinal microgliosis due to resident microglial proliferation is required for pain hypersensitivity after peripheral nerve injury. Cell Reports, 2016, 16(3): 605–614.
Crossref Google Scholar
[29]
Gu, N., Eyo, U. B., Murugan, M., Peng, J. Y., Matta, S., Dong, H. L., Wu, L. J. Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain. Brain, Behavior, and Immunity, 2016, 55: 82–92.
Crossref Google Scholar
[30]
Mo, M. S., Eyo, U. B., Xie, M. L., Peng, J. Y., Bosco, D. B., Umpierre, A. D., Zhu, X. Q., Tian, D. S., Xu, P. Y., Wu, L. J. Microglial P2Y12 receptor regulates seizure-induced neurogenesis and immature neuronal projections. The Journal of Neuroscience, 2019, 39(47): 9453–9464.
Crossref Google Scholar
[31]
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity, 2017, 47(3): 566–581.e9.
Crossref Google Scholar
[32]
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B. V., Jacobson, K. A., Kohsaka, S., Inoue, K. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature, 2007, 446(7139): 1091–1095.
Crossref Google Scholar
[33]
Neher, J. J., Neniskyte, U., Hornik, T., Brown, G. C. Inhibition of UDP/P2Y6purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo. Glia, 2014, 62(9): 1463–1475.
Crossref Google Scholar
[34]
Ito, M., Matsuoka, I. Inhibition of P2Y6 receptor-mediated phospholipase C activation and Ca2+ signalling by prostaglandin E2 in J774 murine macrophages. European Journal of Pharmacology, 2015, 749: 124–132.
Crossref Google Scholar
[35]
Uesugi, A., Kataoka, A., Tozaki-Saitoh, H., Koga, Y., Tsuda, M., Robaye, B., Boeynaems, J. M., Inoue, K. Involvement of protein kinase D in uridine diphosphate-induced microglial macropinocytosis and phagocytosis. Glia, 2012, 60(7): 1094–1105.
Crossref Google Scholar
[36]
Xu, Y. T., Hu, W. H., Liu, Y. M., Xu, P. F., Li, Z. C., Wu, R., Shi, X. L., Tang, Y. M. P2Y6 receptor-mediated microglial phagocytosis in radiation-induced brain injury. Molecular Neurobiology, 2016, 53(6): 3552–3564.
Crossref Google Scholar
[37]
Inoue, K. UDP facilitates microglial phagocytosis through P2Y6 receptors. Cell Adhesion & Migration, 2007, 1(3): 131–132.
Crossref Google Scholar
[38]
de Simone, R., Niturad, C. E., de Nuccio, C., Ajmone-Cat, M. A., Visentin, S., Minghetti, L. TGF-β and LPS modulate ADP-induced migration of microglial cells through P2Y1 and P2Y12 receptor expression. Journal of Neurochemistry, 2010, 115(2): 450–459.
Crossref Google Scholar
[39]
Li, H. Q., Chen, C., Dou, Y., Wu, H. J., Liu, Y. J., Lou, H. F., Zhang, J. M., Li, X. M., Wang, H., Duan, S. P2Y4 receptor-mediated pinocytosis contributes to amyloid beta-induced self-uptake by microglia. Molecular and Cellular Biology, 2013, 33(21): 4282–4293.
Crossref Google Scholar
[40]
Stefani, J., Tschesnokowa, O., Parrilla, M., Robaye, B., Boeynaems, J. M., Acker-Palmer, A., Zimmermann, H., Gampe, K. Disruption of the microglial ADP receptor P2Y13 enhances adult hippocampal neurogenesis. Frontiers in Cellular Neuroscience, 2018, 12: 134. .
Crossref Google Scholar
[41]
Zhou, R., Xu, T., Liu, X. H., Chen, Y. S., Kong, D. Y., Tian, H., Yue, M. X., Huang, D. J., Zeng, J. W. Activation of spinal dorsal horn P2Y13 receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain. Journal of Pain Research, 2018, 11: 615–628.
Crossref Google Scholar
[42]
Kyrargyri, V., Madry, C., Rifat, A., Arancibia-Carcamo, I. L., Jones, S. P., Chan, V. T. T., Xu, Y. J., Robaye, B., Attwell, D. P2Y13 receptors regulate microglial morphology, surveillance, and resting levels of interleukin 1β release. Glia, 2020, 68(2): 328–344.
Crossref Google Scholar
[43]
North, R. A. P2X receptors. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2016, 371(1700): 20150427.
Crossref Google Scholar
[44]
North, R. A. Molecular physiology of P2X receptors. Physiological Reviews, 2002, 82(4): 1013–1067.
Crossref Google Scholar
[45]
Jarvis, M. F. The neural-glial purinergic receptor ensemble in chronic pain states. Trends in Neurosciences, 2010, 33(1): 48–57.
Crossref Google Scholar
[46]
Trang, T., Beggs, S., Salter, M. W. ATP receptors gate microglia signaling in neuropathic pain. Experimental Neurology, 2012, 234(2): 354–361.
Crossref Google Scholar
[47]
Tsuda, M. Microglia in the spinal cord and neuropathic pain. Journal of Diabetes Investigation, 2016, 7(1): 17–26.
Crossref Google Scholar
[48]
Masuda, T., Iwamoto, S., Yoshinaga, R., Tozaki-Saitoh, H., Nishiyama, A., Mak, T. W., Tamura, T., Tsuda, M., Inoue, K. Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain. Nature Communications, 2014, 5: 3771.
Crossref Google Scholar
[49]
Tsuda, M., Shigemoto-Mogami, Y., Koizumi, S., Mizokoshi, A., Kohsaka, S., Salter, M. W., Inoue, K. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature, 2003, 424(6950): 778–783.
Crossref Google Scholar
[50]
Zheng, Z. C., Du, X. J., Zhang, K. G., Wang, X. Y., Chen, Y. X., Kuang, N. F., Fan, T., Sun, B. L. Olfactory ensheathing cell transplantation inhibits P2X4 receptor overexpression in spinal cord injury rats with neuropathic pain. Neuroscience Letters, 2017, 651: 171–176.
Crossref Google Scholar
[51]
Jin, X. H., Wang, L. N., Zuo, J. L., Yang, J. P., Liu, S. L. P2X4 receptor in the dorsal horn partially contributes to brain-derived neurotrophic factor oversecretion and toll-like receptor-4 receptor activation associated with bone cancer pain. Journal of Neuroscience Research, 2014, 92(12): 1690–1702.
Crossref Google Scholar
[52]
Almeida, C., DeMaman, A., Kusuda, R., Cadetti, F., Ravanelli, M. I., Queiroz, A. L., Sousa, T. A., Zanon, S., Silveira, L. R., Lucas, G. Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain. PAIN, 2015, 156(3): 504–513.
Crossref Google Scholar
[53]
Franke, H., Schepper, C., Illes, P., Krügel, U. Involvement of P2X and P2Y receptors in microglial activation in vivo. Purinergic Signalling, 2007, 3(4): 435–445.
Crossref Google Scholar
[54]
Horvath, R. J., DeLeo, J. A. Morphine enhances microglial migration through modulation of P2X4 receptor signaling. The Journal of Neuroscience, 2009, 29(4): 998–1005.
Crossref Google Scholar
[55]
Vázquez-Villoldo, N., Domercq, M., Martín, A., Llop, J., Gómez-Vallejo, V., Matute, C. P2X4 receptors control the fate and survival of activated microglia. Glia, 2014, 62(2): 171–184.
Crossref Google Scholar
[56]
Puchałowicz, K., Tarnowski, M., Baranowska-Bosiacka, I., Chlubek, D., Dziedziejko, V. P2X and P2Y receptors—role in the pathophysiology of the nervous system. International Journal of Molecular Sciences, 2014, 15(12): 23672–23704.
Crossref Google Scholar
[57]
Gordon, J. L. Extracellular ATP: Effects, sources and fate. The Biochemical Journal, 1986, 233(2): 309–319.
Crossref Google Scholar
[58]
Witting, A., Walter, L., Wacker, J., Möller, T., Stella, N. P2X7 receptors control 2-arachidonoylglycerol production by microglial cells. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(9): 3214–3219.
Crossref Google Scholar
[59]
Masuch, A., Shieh, C. H., van Rooijen, N., van Calker, D., Biber, K. Mechanism of microglia neuroprotection: Involvement of P2X7, TNFα, and valproic acid. Glia, 2016, 64(1): 76–89.
Crossref Google Scholar
[60]
Parvathenani, L. K., Tertyshnikova, S., Greco, C. R., Roberts, S. B., Robertson, B., Posmantur, R. P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease. Journal of Biological Chemistry, 2003, 278(15): 13309–13317.
Crossref Google Scholar
[61]
Sanz, J. M., Virgilio, F. D. Kinetics and mechanism of ATP-dependent IL-1β release from microglial cells. The Journal of Immunology, 2000, 164(9): 4893–4898.
Crossref Google Scholar
[62]
Yiangou, Y., Facer, P., Durrenberger, P., Chessell, I. P., Naylor, A., Bountra, C., Banati, R. R., Anand, P. COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurology, 2006, 6: 12.
Crossref Google Scholar
[63]
Shieh, C. H., Heinrich, A., Serchov, T., van Calker, D., Biber, K. P2X7-dependent, but differentially regulated release of IL-6, CCL2, and TNF-α in cultured mouse microglia. Glia, 2014, 62(4): 592–607.
Crossref Google Scholar
[64]
Franke, H., Günther, A., Grosche, J., Schmidt, R., Rossner, S., Reinhardt, R., Faber-Zuschratter, H., Schneider, D., Illes, P. P2X7 receptor expression after ischemia in the cerebral cortex of rats. Journal of Neuropathology & Experimental Neurology, 2004, 63(7): 686–699.
Crossref Google Scholar
[65]
McLarnon, J. G., Ryu, J. K., Walker, D. G., Choi, H. B. Upregulated expression of purinergic P2X7 receptor in alzheimer disease and amyloid-β peptide-treated microglia and in peptide-injected rat hippocampus. Journal of Neuropathology & Experimental Neurology, 2006, 65(11): 1090–1097.
Crossref Google Scholar
[66]
Li, J., Li, X. N., Jiang, X., Yang, M., Yang, R., Burnstock, G., Xiang, Z. H., Yuan, H. B. Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats. Purinergic Signalling, 2017, 13(1): 13–26.
Crossref Google Scholar
[67]
van Hove, H., Martens, L., Scheyltjens, I., de Vlaminck, K., Pombo Antunes, A. R., de Prijck, S., Vandamme, N., de Schepper, S., van Isterdael, G., Scott, C. L. et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nature Neuroscience, 2019, 22(6): 1021–1035.
Crossref Google Scholar
[68]
Garré, J. M., Silva, H. M., Lafaille, J. J., Yang, G. P2X7 receptor inhibition ameliorates dendritic spine pathology and social behavioral deficits in Rett syndrome mice. Nature Communications, 2020, 11: 1784.
Crossref Google Scholar
[69]
Ralevic, V., Burnstock, G. Receptors for purines and pyrimidines. Pharmacological Reviews, 1998, 50(3): 413–492.
Google Scholar
[70]
Chen, J. F., Lee, C. F., Chern, Y. Adenosine receptor neurobiology: Overview. International Review of Neurobiology, 2014, 119: 1–49.
Crossref Google Scholar
[71]
Wollmer, M. A., Lucius, R., Wilms, H., Held-Feindt, J., Sievers, J., Mentlein, R. ATP and adenosine induce ramification of microglia in vitro. Journal of Neuroimmunology, 2001, 115(1–2): 19–27.
Crossref Google Scholar
[72]
Orr, A. G., Orr, A. L., Li, X. J., Gross, R. E., Traynelis, S. F. Adenosine A2A receptor mediates microglial process retraction. Nature Neuroscience, 2009, 12(7): 872–878.
Crossref Google Scholar
[73]
Gyoneva, S., Shapiro, L., Lazo, C., Garnier-Amblard, E., Smith, Y., Miller, G. W., Traynelis, S. F. Adenosine A2A receptor antagonism reverses inflammation-induced impairment of microglial process extension in a model of Parkinson's disease. Neurobiology of Disease, 2014, 67: 191–202.
Crossref Google Scholar
[74]
Trincavelli, M. L., Melani, A., Guidi, S., Cuboni, S., Cipriani, S., Pedata, F., Martini, C. Regulation of A2A adenosine receptor expression and functioning following permanent focal ischemia in rat brain. Journal of Neurochemistry, 2007, 104(2): 479–490.
Crossref Google Scholar
[75]
Gyoneva, S., Orr, A. G., Traynelis, S. F. Differential regulation of microglial motility by ATP/ADP and adenosine. Parkinsonism & Related Disorders, 2009, 15: S195–S199.
Crossref Google Scholar
[76]
Fiebich, B. L., Biber, K., Lieb, K., van Calker, D., Berger, M., Bauer, J., Gebicke-Haerter, P. J. Cyclooxygenase-2 expression in rat microglia is induced by adenosine A2a-receptors. Glia, 1996, 18(2): 152–180.
Crossref
[77]
Saura, J., Angulo, E., Ejarque, A., Casado, V., Tusell, J. M., Moratalla, R., Chen, J. F., Schwarzschild, M. A., Lluis, C., Franco, R. et al. Adenosine A2A receptor stimulation potentiates nitric oxide release by activated microglia. Journal of Neurochemistry, 2005, 95(4): 919–929.
Crossref Google Scholar
[78]
Teismann, P., Vila, M., Choi, D. K., Tieu, K., Wu, D. C., Jackson-Lewis, V., Przedborski, S. COX-2 and neurodegeneration in Parkinson's disease. Annals of the New York Academy of Sciences, 2003, 991: 272–277.
Crossref Google Scholar
[79]
Ouyang, X. S., Ghani, A., Malik, A., Wilder, T., Colegio, O. R., Flavell, R. A., Cronstein, B. N., Mehal, W. Z. Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway. Nature Communications, 2013, 4: 2909.
Crossref Google Scholar
[80]
Li, Z. H., Li, W., Li, Q., Tang, M. K. Extracellular nucleotides and adenosine regulate microglial motility and their role in cerebral ischemia. Acta Pharmaceutica Sinica B, 2013, 3(4): 205–212.
Crossref Google Scholar
[81]
Ahmad, S., Fatteh, N., El-Sherbiny, N. M., Naime, M., Ibrahim, A. S., El-Sherbini, A. M., El-Shafey, S. A., Khan, S., Fulzele, S., Gonzales, J. et al. Potential role of A2A adenosine receptor in traumatic optic neuropathy. Journal of Neuroimmunology, 2013, 264(1–2): 54–64.
Crossref Google Scholar
[82]
Colella, M., Zinni, M., Pansiot, J., Cassanello, M., Mairesse, J., Ramenghi, L., Baud, O. Modulation of microglial activation by adenosine A2a receptor in animal models of perinatal brain injury. Frontiers in Neurology, 2018, 9: 605. .
Crossref Google Scholar
[83]
Luongo, L., Guida, F., Imperatore, R., Napolitano, F., Gatta, L., Cristino, L., Giordano, C., Siniscalco, D., di Marzo, V., Bellini, G. et al. The A1 adenosine receptor as a new player in microglia physiology. Glia, 2014, 62(1): 122–132.
Crossref Google Scholar
[84]
Synowitz, M., Glass, R., Färber, K., Markovic, D., Kronenberg, G., Herrmann, K., Schnermann, J., Nolte, C., van Rooijen, N., Kiwit, J. et al. A1 adenosine receptors in microglia control glioblastoma-host interaction. Cancer Research, 2006, 66(17): 8550–8557.
Crossref Google Scholar
[85]
Tsutsui, S. A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. Journal of Neuroscience, 2004, 24(6): 1521–1529.
Crossref Google Scholar
[86]
Terayama, R., Tabata, M., Maruhama, K., Iida, S. A3 adenosine receptor agonist attenuates neuropathic pain by suppressing activation of microglia and convergence of nociceptive inputs in the spinal dorsal horn. Experimental Brain Research, 2018, 236(12): 3203–3213.
Crossref Google Scholar
[87]
Merighi, S., Borea, P. A., Stefanelli, A., Bencivenni, S., Castillo, C. A., Varani, K., Gessi, S. A2a and a2b adenosine receptors affect HIF-1α signaling in activated primary microglial cells. Glia, 2015, 63(11): 1933–1952.
Crossref Google Scholar
[88]
Pedata, F., Corsi, C., Melani, A., Bordoni, F., Latini, S. Adenosine extracellular brain concentrations and role of A2A receptors in ischemia. Annals of the New York Academy of Sciences, 2006, 939(1): 74–84.
Crossref Google Scholar
[89]
van der Putten, C., Zuiderwijk-Sick, E. A., van Straalen, L., de Geus, E. D., Boven, L. A., Kondova, I., IJzerman, A. P., Bajramovic, J. J. Differential expression of adenosine A3 receptors controls adenosine A2A receptor-mediated inhibition of TLR responses in microglia. The Journal of Immunology, 2009, 182(12): 7603–7612.
Crossref Google Scholar
[90]
Ohsawa, K., Sanagi, T., Nakamura, Y., Suzuki, E., Inoue, K., Kohsaka, S. Adenosine A3 receptor is involved in ADP-induced microglial process extension and migration. Journal of Neurochemistry, 2012, 121(2): 217–227.
Crossref Google Scholar
Stress and Brain
Volume 1 Issue 1,
September 2021
Pages 46-58
DOI: 10.26599/SAB.2020.9060005
Cite this article:
Hu Y, Gao Z. The role of purinergic signaling in microglial responses. Stress and Brain, 2021, 1(1): 46-58. https://doi.org/10.26599/SAB.2020.9060005

2569

Views

312

Downloads

1

Crossref

Altmetrics
Received: 02 March 2020
Revised: 28 June 2020
Accepted: 22 July 2020
Published: 10 March 2021
© The Author(s) 2020

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission.
Return