{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T01:27:44Z","timestamp":1783733264564,"version":"3.55.0"},"reference-count":84,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T00:00:00Z","timestamp":1516233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2013\u20100795"],"award-info":[{"award-number":["2013\u20100795"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2014\u20101094"],"award-info":[{"award-number":["2014\u20101094"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2018,2]]},"abstract":"Abstract<\/jats:title>Astrocytes participate in the development and resolution of neuroinflammation in numerous ways, including the release of cytokines and growth factors. Among many, astrocytes release transforming growth factors beta (TGF<\/jats:styled-content>\u2010\u03b2) TGF<\/jats:styled-content>\u2010\u03b21, TGF<\/jats:styled-content>\u2010\u03b22 and TGF<\/jats:styled-content>\u2010\u03b23. TGF<\/jats:styled-content>\u2010\u03b21 is the most studied isoform, while production and release of TGF<\/jats:styled-content>\u2010\u03b22 and TGF<\/jats:styled-content>\u2010\u03b23 by astrocytes have been poorly characterized. Here, we report that purified cultures of hippocampal astrocytes produce mainly TGF<\/jats:styled-content>\u2010\u03b23 followed by TGF<\/jats:styled-content>\u2010\u03b22 and TGF<\/jats:styled-content>\u2010\u03b21. Furthermore, astrocytes release principally the active form of TGF<\/jats:styled-content>\u2010\u03b23 over the other two. Changes in release of TGF<\/jats:styled-content>\u2010\u03b2 were sensitive to the calcineurin (CaN) inhibitor FK<\/jats:styled-content>506. Starvation had no effect on TGF<\/jats:styled-content>\u2010\u03b21 and TGF<\/jats:styled-content>\u2010\u03b23 while TGF<\/jats:styled-content>\u2010\u03b22 mRNA<\/jats:styled-content> was significantly up\u2010regulated in a CaN\u2010dependent manner. We further investigated production and release of astroglial TGF<\/jats:styled-content>\u2010\u03b2 in Alzheimer's disease\u2010related conditions. Oligomeric \u03b2\u2010amyloid (A\u03b2) down\u2010regulated TGF<\/jats:styled-content>\u2010\u03b21, while up\u2010regulating TGF<\/jats:styled-content>\u2010\u03b22 and TGF<\/jats:styled-content>\u2010\u03b23, in a CaN\u2010dependent manner. In cultured hippocampal astrocytes from 3xTg\u2010AD<\/jats:styled-content> mice, TGF<\/jats:styled-content>\u2010\u03b22 and TGF<\/jats:styled-content>\u2010\u03b23, but not TGF<\/jats:styled-content>\u2010\u03b21, were up\u2010regulated, and this was CaN\u2010independent. In hippocampal tissues from symptomatic 3xTg\u2010AD<\/jats:styled-content> mice, TGF<\/jats:styled-content>\u2010\u03b22 was up\u2010regulated with respect to control mice. Finally, treatment with recombinant TGF<\/jats:styled-content>\u2010\u03b2s showed that TGF<\/jats:styled-content>\u2010\u03b22 and TGF<\/jats:styled-content>\u2010\u03b23 significantly reduced PSD<\/jats:styled-content>95 protein in cultured hippocampal neurons, and this effect was paralleled by conditioned media from A\u03b2\u2010treated astrocytes or from astrocytes from 3xTg\u2010AD<\/jats:styled-content> mice. Taken together, our data suggest that TGF<\/jats:styled-content>\u2010\u03b22 and TGF<\/jats:styled-content>\u2010\u03b23 are produced by astrocytes in a CaN\u2010dependent manner and should be investigated further in the context of astrocyte\u2010mediated neurodegeneration.<\/jats:p>","DOI":"10.1111\/ejn.13819","type":"journal-article","created":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T14:54:41Z","timestamp":1514472881000},"page":"211-221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["TGF<\/scp>\u2010\u03b22 and TGF<\/scp>\u2010\u03b23 from cultured \u03b2\u2010amyloid\u2010treated or 3xTg\u2010AD<\/scp>\u2010derived astrocytes may mediate astrocyte\u2013neuron communication"],"prefix":"10.1111","volume":"47","author":[{"given":"Laura","family":"Tapella","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Cerruti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Biocotino","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Stevano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Rocchio","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Canonico","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagrazia","family":"Grilli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando A.","family":"Genazzani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-2654","authenticated-orcid":false,"given":"Dmitry","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 degli Studi del Piemonte Orientale \u201cAmedeo Avogadro\u201d 28100 Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-007-0466-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00278"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000089137"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977199009037500"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.051272"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700243200"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4178-07.2008"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2009.00115.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1230-6"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.12.082"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090379"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90192-9"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02648-0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12473"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2014.07.008"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"6797","DOI":"10.1523\/JNEUROSCI.3351-16.2017","article-title":"Astrocyte transforming growth factor beta 1 protects synapses against A\u03b2 oligomers in Alzheimer's disease model","volume":"3","author":"Diniz L.P.","year":"2017","journal-title":"J. Neurosci."},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu280"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.08.086"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1002-07.2007"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(97)00066-X"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-014-0158-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06640.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5797"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1736-09.2009"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208925"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2005.04.001"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.05.005"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.145"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/4789"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20149"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.21.9304-9317.2005"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20804"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8639-3"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(93)90156-B"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.5603\/EP.2013.0022"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"19128","DOI":"10.1016\/S0021-9258(17)30634-8","article-title":"Structural and functional characterization of the transforming growth factor beta 3 promoter. A cAMP\u2010responsive element regulates basal and induced transcription","volume":"265","author":"Lafyatis R.","year":"1990","journal-title":"J. Biol. Chem."},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2002.1121"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2015.02.018"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2010.09.011"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22502"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/112_2014_19"},{"key":"e_1_2_10_43_1","first-page":"122","article-title":"From pathology to physiology of calcineurin signalling in astrocytes","volume":"2","author":"Lim D.","year":"2016","journal-title":"Opera Med Physiol"},{"key":"e_1_2_10_44_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2174\/1567205013666151116130104","article-title":"Calcium signalling toolkits in astrocytes and spatio\u2010temporal progression of Alzheimer's disease","volume":"13","author":"Lim D.","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)90804-V"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2014.903947"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.753"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.1080320204"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2016.09.018"},{"key":"e_1_2_10_50_1","first-page":"559","article-title":"The transforming growth factor\u2010betas: multifaceted regulators of the development and maintenance of skeletal muscles, motoneurons and Schwann cells","volume":"46","author":"McLennan I.S.","year":"2002","journal-title":"Int. J. Dev. Biol."},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205013666160125113509"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(99)00029-5"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207450903139689"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00434-3"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.06.004"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.07.008"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07664.x"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.07.012"},{"key":"e_1_2_10_59_1","first-page":"245","article-title":"Neuroimmunomodulation by calcineurin in aging and Alzheimer's disease","volume":"1","author":"Reese L.C.","year":"2010","journal-title":"Aging Dis."},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015911798376316"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.1.309"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2014.09.004"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11295"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22227"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.20546"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720506779025297"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2005.04.006"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-9-48"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1996.0200"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.08.039"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1042\/AN20120010"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-014-1403-2"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22422"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.06.015"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00475-9"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R115.657262"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2013.0220"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720506777632916"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/39321"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64713-X"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06382.x"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/747343"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-016-0054-4"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1042\/AN20110061"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejn.13819","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.13819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T17:43:11Z","timestamp":1695750191000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.13819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,18]]},"references-count":84,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/ejn.13819"],"URL":"https:\/\/doi.org\/10.1111\/ejn.13819","archive":["Portico"],"relation":{},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,18]]},"assertion":[{"value":"2017-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}