{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:39:51Z","timestamp":1790721591880,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Research Council","award":["MR\/P025811\/1"],"award-info":[{"award-number":["MR\/P025811\/1"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Brain Struct Funct"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inward rectifying potassium channels (Kir) are a large family of ion channels that play key roles in ion homeostasis in oligodendrocytes, the myelinating cells of the central nervous system (CNS). Prominent expression of Kir4.1 has been indicated in oligodendrocytes, but the extent of expression of other Kir subtypes is unclear. Here, we used qRT-PCR to determine expression of Kir channel transcripts in the mouse optic nerve, a white matter tract comprising myelinated axons and the glia that support them. A novel finding was the high relative expression of Kir7.1, comparable to that of Kir4.1, the main glial Kir channel. Significantly, Kir7.1 immunofluorescence labelling in optic nerve sections and in isolated cells was localised to oligodendrocyte somata. Kir7.1 are known as a K<jats:sup>+<\/jats:sup>transporting channels and, using patch clamp electrophysiology and the Kir7.1 blocker VU590, we demonstrated Kir7.1 channels carry a significant proportion of the whole cell potassium conductance in oligodendrocytes isolated from mouse optic nerves. Notably, oligodendrocytes are highly susceptible to ischemia\/hypoxia and this is due at least in part to disruption of ion homeostasis. A key finding of this study is that blockade of Kir7.1 with VU590 compromised oligodendrocyte cell integrity and compounds oligodendroglial loss in ischemia\/hypoxia in the oxygen\u2013glucose deprivation (OGD) model in isolated intact optic nerves. These data reveal Kir7.1 channels are molecularly and functionally expressed in oligodendrocytes and play an important role in determining oligodendrocyte survival and myelin integrity.<\/jats:p>","DOI":"10.1007\/s00429-020-02043-4","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T15:02:37Z","timestamp":1582297357000},"page":"925-934","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A critical role for the inward rectifying potassium channel Kir7.1 in oligodendrocytes of the mouse optic nerve"],"prefix":"10.1007","volume":"225","author":[{"given":"Maria","family":"Papanikolaou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-0746","authenticated-orcid":false,"given":"Arthur M.","family":"Butt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,21]]},"reference":[{"issue":"4","key":"2043_CR1","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/glia.22299","volume":"60","author":"V Bay","year":"2012","unstructured":"Bay V, Butt AM (2012) Relationship between glial potassium regulation and axon excitability: a role for glial Kir4.1 channels. Glia 60(4):651\u2013660","journal-title":"Glia"},{"issue":"1","key":"2043_CR2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1124\/mol.110.066928","volume":"79","author":"G Bhave","year":"2011","unstructured":"Bhave G, Chauder BA, Liu W, Dawson ES, Kadakia R, Nguyen TT, Lewis LM, Meiler J, Weaver CD, Satlin LM, Lindsley CW, Denton JS (2011) Development of a selective small-molecule inhibitor of Kir1.1, the renal outer medullary potassium channel. Mol Pharmacol 79(1):42\u201350","journal-title":"Mol Pharmacol"},{"issue":"1","key":"2043_CR3","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.expneurol.2006.05.009","volume":"202","author":"S Bolton","year":"2006","unstructured":"Bolton S, Butt AM (2006) Cyclic AMP-mediated regulation of the resting membrane potential in myelin-forming oligodendrocytes in the isolated intact rat optic nerve. Exp Neurol 202(1):36\u201343","journal-title":"Exp Neurol"},{"issue":"1","key":"2043_CR4","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1073\/pnas.76.1.514","volume":"76","author":"JE Bottenstein","year":"1979","unstructured":"Bottenstein JE, Sato GH (1979) Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci USA 76(1):514\u2013517","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"2043_CR100","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3390\/neuroglia1010012","volume":"1","author":"C Brasko","year":"2018","unstructured":"Brasko C, Butt AM (2018) Expression of Kir2.1 inward rectifying potassium channels in optic nerve glia: evidence for heteromeric association with Kir4.1 and Kir5.1. Neuroglia 1(1):176\u2013187","journal-title":"Neuroglia"},{"issue":"1","key":"2043_CR5","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s00429-016-1199-8","volume":"222","author":"C Brasko","year":"2017","unstructured":"Brasko C, Hawkins V, De La Rocha IC, Butt AM (2017) Expression of Kir4.1 and Kir5.1 inwardly rectifying potassium channels in oligodendrocytes, the myelinating cells of the CNS. Brain Struct Funct 222(1):41\u201359","journal-title":"Brain Struct Funct"},{"issue":"2","key":"2043_CR6","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.semcdb.2011.02.023","volume":"22","author":"AM Butt","year":"2011","unstructured":"Butt AM (2011) ATP: a ubiquitous gliotransmitter integrating neuron-glial networks. Semin Cell Dev Biol 22(2):205\u2013213","journal-title":"Semin Cell Dev Biol"},{"issue":"1","key":"2043_CR7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/j.1582-4934.2006.tb00289.x","volume":"10","author":"AM Butt","year":"2006","unstructured":"Butt AM, Kalsi A (2006) Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions. J Cell Mol Med 10(1):33\u201344","journal-title":"J Cell Mol Med"},{"issue":"11","key":"2043_CR8","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1002\/glia.22674","volume":"62","author":"AM Butt","year":"2014","unstructured":"Butt AM, Fern RF, Matute C (2014) Neurotransmitter signaling in white matter. Glia 62(11):1762\u20131779","journal-title":"Glia"},{"issue":"10","key":"2043_CR9","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1177\/1933719116687657","volume":"24","author":"DJ Crankshaw","year":"2017","unstructured":"Crankshaw DJ, Crosby DA, Morrison JJ (2017) Effects of the KIR7.1 blocker VU590 on spontaneous and agonist-induced contractions of human pregnant myometrium. Reprod Sci 24(10):1402\u20131409","journal-title":"Reprod Sci"},{"issue":"6","key":"2043_CR10","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1046\/j.1523-1755.2001.00735.x","volume":"59","author":"C Derst","year":"2001","unstructured":"Derst C, Hirsch JR, Preisig-Muller R, Wischmeyer E, Karschin A, Doring F, Thomzig A, Veh RW, Schlatter E, Kummer W, Daut J (2001) Cellular localization of the potassium channel Kir7.1 in guinea pig and human kidney. Kidney Int 59(6):2197\u20132205","journal-title":"Kidney Int"},{"issue":"21","key":"2043_CR11","doi-asserted-by":"publisher","first-page":"8625","DOI":"10.1523\/JNEUROSCI.18-21-08625.1998","volume":"18","author":"F Doring","year":"1998","unstructured":"Doring F, Derst C, Wischmeyer E, Karschin C, Schneggenburger R, Daut J, Karschin A (1998) The epithelial inward rectifier channel Kir7.1 displays unusual K+ permeation properties. J Neurosci 18(21):8625\u20138636","journal-title":"J Neurosci"},{"issue":"11","key":"2043_CR12","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1002\/glia.22722","volume":"62","author":"RF Fern","year":"2014","unstructured":"Fern RF, Matute C, Stys PK (2014) White matter injury: Ischemic and nonischemic. Glia 62(11):1780\u20131789","journal-title":"Glia"},{"issue":"7545","key":"2043_CR13","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/nature14051","volume":"520","author":"M Ghamari-Langroudi","year":"2015","unstructured":"Ghamari-Langroudi M, Digby GJ, Sebag JA, Millhauser GL, Palomino R, Matthews R, Gillyard T, Panaro BL, Tough IR, Cox HM, Denton JS, Cone RD (2015) G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature 520(7545):94\u201398","journal-title":"Nature"},{"key":"2043_CR14","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.nbd.2013.03.016","volume":"55","author":"V Hawkins","year":"2013","unstructured":"Hawkins V, Butt A (2013) TASK-1 channels in oligodendrocytes: a role in ischemia mediated disruption. Neurobiol Dis 55:87\u201394","journal-title":"Neurobiol Dis"},{"issue":"1","key":"2043_CR15","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1152\/physrev.00021.2009","volume":"90","author":"H Hibino","year":"2010","unstructured":"Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y (2010) Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90(1):291\u2013366","journal-title":"Physiol Rev"},{"issue":"3","key":"2043_CR16","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.mcn.2005.08.011","volume":"30","author":"PG Hirrlinger","year":"2005","unstructured":"Hirrlinger PG, Scheller A, Braun C, Quintela-Schneider M, Fuss B, Hirrlinger J, Kirchhoff F (2005) Expression of reef coral fluorescent proteins in the central nervous system of transgenic mice. Mol Cell Neurosci 30(3):291\u2013303","journal-title":"Mol Cell Neurosci"},{"key":"2043_CR17","doi-asserted-by":"publisher","unstructured":"Ichihara YG, Okabe M, Iga K, Tanaka Y, Musha K , Ito K (2008) Color universal design: the selection of four easily distinguishable colors for all color vision types. In: Proceedings, color imaging XIII: processing, hardcopy, and applications, vol 6807. https:\/\/doi.org\/10.1117\/12.765420","DOI":"10.1117\/12.765420"},{"issue":"6","key":"2043_CR18","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/j.0021-8782.2004.00288.x","volume":"204","author":"AS Kalsi","year":"2004","unstructured":"Kalsi AS, Greenwood K, Wilkin G, Butt AM (2004) Kir4.1 expression by astrocytes and oligodendrocytes in CNS white matter: a developmental study in the rat optic nerve. J Anat 204(6):475\u2013485","journal-title":"J Anat"},{"issue":"2","key":"2043_CR19","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nn1620","volume":"9","author":"N Kessaris","year":"2006","unstructured":"Kessaris N, Fogarty M, Iannarelli P, Grist M, Wegner M, Richardson WD (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 9(2):173\u2013179","journal-title":"Nat Neurosci"},{"issue":"3","key":"2043_CR20","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1124\/mol.117.108472","volume":"92","author":"SV Kharade","year":"2017","unstructured":"Kharade SV, Sheehan JH, Figueroa EE, Meiler J, Denton JS (2017) Pore polarity and charge determine differential block of Kir1.1 and Kir7.1 potassium channels by small-molecule inhibitor VU590. Mol Pharmacol 92(3):338\u2013346","journal-title":"Mol Pharmacol"},{"issue":"5","key":"2043_CR21","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/S0896-6273(00)80480-8","volume":"20","author":"G Krapivinsky","year":"1998","unstructured":"Krapivinsky G, Medina I, Eng L, Krapivinsky L, Yang Y, Clapham DE (1998) A novel inward rectifier K+ channel with unique pore properties. Neuron 20(5):995\u20131005","journal-title":"Neuron"},{"issue":"6","key":"2043_CR22","doi-asserted-by":"publisher","first-page":"488","DOI":"10.4161\/19336950.2014.959809","volume":"8","author":"M Kumar","year":"2014","unstructured":"Kumar M, Pattnaik BR (2014) Focus on Kir7.1: physiology and channelopathy. Channels (Austin) 8(6):488\u2013495","journal-title":"Channels (Austin)"},{"issue":"5","key":"2043_CR23","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1124\/mol.109.059840","volume":"76","author":"LM Lewis","year":"2009","unstructured":"Lewis LM, Bhave G, Chauder BA, Banerjee S, Lornsen KA, Redha R, Fallen K, Lindsley CW, Weaver CD, Denton JS (2009) High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1. Mol Pharmacol 76(5):1094\u20131103","journal-title":"Mol Pharmacol"},{"issue":"4","key":"2043_CR24","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1152\/physrev.1999.79.4.1431","volume":"79","author":"P Lipton","year":"1999","unstructured":"Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79(4):1431\u20131568","journal-title":"Physiol Rev"},{"issue":"7049","key":"2043_CR25","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/nature03837","volume":"436","author":"T Matsuoka","year":"2005","unstructured":"Matsuoka T, Ahlberg PE, Kessaris N, Iannarelli P, Dennehy U, Richardson WD, McMahon AP, Koentges G (2005) Neural crest origins of the neck and shoulder. Nature 436(7049):347\u2013355","journal-title":"Nature"},{"issue":"9","key":"2043_CR26","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.15252\/emmm.201403944","volume":"6","author":"C McCloskey","year":"2014","unstructured":"McCloskey C, Rada C, Bailey E, McCavera S, van den Berg HA, Atia J, Rand DA, Shmygol A, Chan YW, Quenby S, Brosens JJ, Vatish M, Zhang J, Denton JS, Taggart MJ, Kettleborough C, Tickle D, Jerman J, Wright P, Dale T, Kanumilli S, Trezise DJ, Thornton S, Brown P, Catalano R, Lin N, England SK, Blanks AM (2014) The inwardly rectifying K+ channel KIR7.1 controls uterine excitability throughout pregnancy. EMBO Mol Med 6(9):1161\u20131174","journal-title":"EMBO Mol Med"},{"issue":"Pt 2","key":"2043_CR27","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1042\/bj3420329","volume":"342","author":"N Nakamura","year":"1999","unstructured":"Nakamura N, Suzuki Y, Sakuta H, Ookata K, Kawahara K, Hirose S (1999) Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+, K+-ATPase. Biochem J 342(Pt 2):329\u2013336","journal-title":"Biochem J"},{"issue":"15","key":"2043_CR28","doi-asserted-by":"publisher","first-page":"5429","DOI":"10.1523\/JNEUROSCI.21-15-05429.2001","volume":"21","author":"C Neusch","year":"2001","unstructured":"Neusch C, Rozengurt N, Jacobs RE, Lester HA, Kofuji P (2001) Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J Neurosci 21(15):5429\u20135438","journal-title":"J Neurosci"},{"issue":"11","key":"2043_CR29","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1681\/ASN.V11111987","volume":"11","author":"K Ookata","year":"2000","unstructured":"Ookata K, Tojo A, Suzuki Y, Nakamura N, Kimura K, Wilcox CS, Hirose S (2000) Localization of inward rectifier potassium channel Kir7.1 in the basolateral membrane of distal nephron and collecting duct. J Am Soc Nephrol 11(11):1987\u20131994","journal-title":"J Am Soc Nephrol"},{"issue":"7","key":"2043_CR30","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1007\/s00429-017-1380-8","volume":"222","author":"M Papanikolaou","year":"2017","unstructured":"Papanikolaou M, Lewis A, Butt AM (2017) Store-operated calcium entry is essential for glial calcium signalling in CNS white matter. Brain Struct Funct 222(7):2993\u20133005","journal-title":"Brain Struct Funct"},{"issue":"5","key":"2043_CR31","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1111\/joa.13048","volume":"235","author":"M Papanikolaou","year":"2019","unstructured":"Papanikolaou M, Lewis A, Butt AM (2019) Glial and neuronal expression of the Inward Rectifying Potassium Channel Kir7.1 in the adult mouse brain. J Anat 235(5):984\u2013996","journal-title":"J Anat"},{"issue":"8","key":"2043_CR32","doi-asserted-by":"publisher","first-page":"e71744","DOI":"10.1371\/journal.pone.0071744","volume":"8","author":"BR Pattnaik","year":"2013","unstructured":"Pattnaik BR, Tokarz S, Asuma MP, Schroeder T, Sharma A, Mitchell JC, Edwards AO, Pillers DA (2013) Snowflake vitreoretinal degeneration (SVD) mutation R162W provides new insights into Kir7.1 ion channel structure and function. PLoS ONE 8(8):e71744","journal-title":"PLoS ONE"},{"key":"2043_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2174\/1389450117666160711154529","volume":"17","author":"A Rivera","year":"2016","unstructured":"Rivera A, Ilaria V, Arthur MB (2016) A central role for ATP signaling in Glial interactions in the CNS. Curr Drug Targets 17:1\u20135","journal-title":"Curr Drug Targets"},{"key":"2043_CR34","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.exer.2018.07.014","volume":"176","author":"D Roman","year":"2018","unstructured":"Roman D, Zhong H, Yaklichkin S, Chen R, Mardon G (2018) Conditional loss of Kcnj13 in the retinal pigment epithelium causes photoreceptor degeneration. Exp Eye Res 176:219\u2013226","journal-title":"Exp Eye Res"},{"issue":"7071","key":"2043_CR35","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1038\/nature04301","volume":"438","author":"MG Salter","year":"2005","unstructured":"Salter MG, Fern R (2005) NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438(7071):1167\u20131171","journal-title":"Nature"},{"key":"2043_CR36","doi-asserted-by":"publisher","first-page":"36428","DOI":"10.7554\/eLife.36428","volume":"7","author":"L Schirmer","year":"2018","unstructured":"Schirmer L, Mobius W, Zhao C, Cruz-Herranz A, Haim LB, Cordano C, Shiow LR, Kelley KW, Sadowski B, Timmons G, Probstel AK, Wright JN, Sin JH, Devereux M, Morrison DE, Chang SM, Sabeur K, Green AJ, Nave KA, Franklin RJ, Rowitch DH (2018) Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity. Elife 7:36428","journal-title":"Elife"},{"issue":"9","key":"2043_CR37","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1038\/sj.jcbfm.9600455","volume":"27","author":"SB Tekkok","year":"2007","unstructured":"Tekkok SB, Ye Z, Ransom BR (2007) Excitotoxic mechanisms of ischemic injury in myelinated white matter. J Cereb Blood Flow Metab 27(9):1540\u20131552","journal-title":"J Cereb Blood Flow Metab"},{"issue":"3","key":"2043_CR38","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.preteyeres.2006.12.002","volume":"26","author":"S Wimmers","year":"2007","unstructured":"Wimmers S, Karl MO, Strauss O (2007) Ion channels in the RPE. Prog Retin Eye Res 26(3):263\u2013301","journal-title":"Prog Retin Eye Res"},{"issue":"7","key":"2043_CR39","doi-asserted-by":"publisher","first-page":"3178","DOI":"10.1167\/iovs.02-1189","volume":"44","author":"D Yang","year":"2003","unstructured":"Yang D, Pan A, Swaminathan A, Kumar G, Hughes BA (2003) Expression and localization of the inwardly rectifying potassium channel Kir7.1 in native bovine retinal pigment epithelium. Invest Ophthalmol Vis Sci 44(7):3178\u20133185","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["Brain Structure and Function"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00429-020-02043-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00429-020-02043-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00429-020-02043-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T06:25:13Z","timestamp":1665901513000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00429-020-02043-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,21]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["2043"],"URL":"https:\/\/doi.org\/10.1007\/s00429-020-02043-4","relation":{},"ISSN":["1863-2653","1863-2661"],"issn-type":[{"value":"1863-2653","type":"print"},{"value":"1863-2661","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,21]]},"assertion":[{"value":"20 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"AB declares that he is co-founder of and shareholder in GliaGenesis Ltd. The authors declare that they have no other conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All applicable international, national, and\/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}