{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T08:09:21Z","timestamp":1773302961114,"version":"3.50.1"},"reference-count":65,"publisher":"Frontiers Media SA","content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"DOI":"10.3389\/fendo.2016.00066","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T12:19:39Z","timestamp":1466079579000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["The Mineralocorticoid Agonist Fludrocortisone Promotes Survival and Proliferation of Adult Hippocampal Progenitors"],"prefix":"10.3389","volume":"7","author":[{"given":"Iacopo","family":"Gesmundo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Villanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Gargantini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Arvat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezio","family":"Ghigo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccarda","family":"Granata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2016,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1210\/edrv.19.3.0331","article-title":"Brain corticosteroid receptor balance in health and disease","volume":"19","author":"De Kloet","year":"1998","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1002\/jnr.490210113","article-title":"Distribution of the mineralocorticoid and the glucocorticoid receptor mRNAs in the rat hippocampus","volume":"21","author":"Van Eekelen","year":"1988","journal-title":"J Neurosci Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/0896-6273(88)90136-5","article-title":"The neuronal mineralocorticoid receptor as a mediator of glucocorticoid response","volume":"1","author":"Arriza","year":"1988","journal-title":"Neuron"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.tins.2007.10.005","article-title":"The coming out of the brain mineralocorticoid receptor","volume":"31","author":"Joels","year":"2008","journal-title":"Trends Neurosci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1126\/science.275.5300.661","article-title":"Regulation of neuronal survival by the serine-threonine protein kinase Akt","volume":"275","author":"Dudek","year":"1997","journal-title":"Science"},{"key":"B6","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1523\/JNEUROSCI.22-09-03673.2002","article-title":"Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein","volume":"22","author":"Nakagawa","year":"2002","journal-title":"J Neurosci"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1111\/j.1460-9568.2011.07606.x","article-title":"CREB in adult neurogenesis \u2013 master and partner in the development of adult-born neurons?","volume":"33","author":"Merz","year":"2011","journal-title":"Eur J Neurosci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1044-7431(03)00082-4","article-title":"IGF-I has a direct proliferative effect in adult hippocampal progenitor cells","volume":"24","author":"Aberg","year":"2003","journal-title":"Mol Cell Neurosci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1002\/dneu.20506","article-title":"PI3K\/Akt and CREB regulate adult neural hippocampal progenitor proliferation and differentiation","volume":"67","author":"Peltier","year":"2007","journal-title":"Dev Neurobiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.mce.2015.11.008","article-title":"Obestatin promotes proliferation and survival of adult hippocampal progenitors and reduces amyloid-beta-induced toxicity","volume":"422","author":"Gargantini","year":"2016","journal-title":"Mol Cell Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/nrn2870","article-title":"GSK3 signalling in neural development","volume":"11","author":"Hur","year":"2010","journal-title":"Nat Rev Neurosci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3389\/fnmol.2014.00028","article-title":"mTOR signaling and its roles in normal and abnormal brain development","volume":"7","author":"Takei","year":"2014","journal-title":"Front Mol Neurosci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1016\/j.cell.2013.05.002","article-title":"Dynamics of hippocampal neurogenesis in adult humans","volume":"153","author":"Spalding","year":"2013","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1152\/physrev.00004.2014","article-title":"Regulation and function of adult neurogenesis: from genes to cognition","volume":"94","author":"Aimone","year":"2014","journal-title":"Physiol Rev"},{"key":"B15","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/0306-4522(94)90224-0","article-title":"Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus","volume":"61","author":"Cameron","year":"1994","journal-title":"Neuroscience"},{"key":"B16","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1523\/JNEUROSCI.17-07-02492.1997","article-title":"Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation","volume":"17","author":"Gould","year":"1997","journal-title":"J Neurosci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2004.07.093","article-title":"Dexamethasone inhibits proliferation of adult hippocampal neurogenesis in vivo and in vitro","volume":"1027","author":"Kim","year":"2004","journal-title":"Brain Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ejphar.2008.01.014","article-title":"Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice","volume":"583","author":"Murray","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.neuron.2009.04.017","article-title":"Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety\/depression","volume":"62","author":"David","year":"2009","journal-title":"Neuron"},{"key":"B20","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.neuroscience.2010.04.023","article-title":"Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats","volume":"168","author":"Brummelte","year":"2010","journal-title":"Neuroscience"},{"key":"B21","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/mp.2011.161","article-title":"Leptin restores adult hippocampal neurogenesis in a chronic unpredictable stress model of depression and reverses glucocorticoid-induced inhibition of GSK-3beta\/beta-catenin signaling","volume":"17","author":"Garza","year":"2011","journal-title":"Mol Psychiatry"},{"key":"B22","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1002\/cne.1297","article-title":"Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone-dependent mechanism","volume":"437","author":"Tanapat","year":"2001","journal-title":"JComp Neurol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1210\/en.2011-2184","article-title":"The protective side of the mineralocorticoid receptor","volume":"153","author":"Gomez-Sanchez","year":"2012","journal-title":"Endocrinology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1093\/embo-reports\/kvd088","article-title":"Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice","volume":"1","author":"Gass","year":"2000","journal-title":"EMBO Rep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1073\/pnas.0503878102","article-title":"Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity","volume":"103","author":"Berger","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1210\/en.2011-1436","article-title":"Mineralocorticoid receptor overexpression facilitates differentiation and promotes survival of embryonic stem cell-derived neurons","volume":"153","author":"Munier","year":"2012","journal-title":"Endocrinology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1111\/j.1460-9568.2007.05427.x","article-title":"Forebrain mineralocorticoid receptor overexpression enhances memory, reduces anxiety and attenuates neuronal loss in cerebral ischaemia","volume":"25","author":"Lai","year":"2007","journal-title":"Eur J Neurosci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/sj.mp.4001679","article-title":"Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation","volume":"10","author":"Crochemore","year":"2005","journal-title":"Mol Psychiatry"},{"key":"B29","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/S0006-8993(02)03042-1","article-title":"The prototypic mineralocorticoid receptor agonist aldosterone influences neurogenesis in the dentate gyrus of the adrenalectomized rat","volume":"947","author":"Fischer","year":"2002","journal-title":"Brain Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"5083","DOI":"10.1210\/jc.2006-0915","article-title":"A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness","volume":"91","author":"Derijk","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1530\/EJE-09-1076","article-title":"Effect of acute and prolonged mineralocorticoid receptor blockade on spontaneous and stimulated hypothalamic-pituitary-adrenal axis in humans","volume":"162","author":"Berardelli","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3233\/JAD-2012-120328","article-title":"Stress hormone leads to memory deficits and altered tau phosphorylation in a model of Alzheimer\u2019s disease","volume":"31","author":"Joshi","year":"2012","journal-title":"J Alzheimers Dis"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/j.neurobiolaging.2012.11.015","article-title":"Deregulation of hypothalamic-pituitary-adrenal axis functions in an Alzheimer\u2019s disease rat model","volume":"34","author":"Brureau","year":"2013","journal-title":"Neurobiol Aging"},{"key":"B34","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic Abeta oligomer and Alzheimer\u2019s disease: an emperor in need of clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat Neurosci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The cellular phase of Alzheimer\u2019s disease","volume":"164","author":"De Strooper","year":"2016","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/j.neurobiolaging.2014.09.008","article-title":"Stimulation of the mineralocorticoid receptor improves memory in young and elderly healthy individuals","volume":"36","author":"Hinkelmann","year":"2015","journal-title":"Neurobiol Aging"},{"key":"B37","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/npp.2014.181","article-title":"Mineralocorticoid receptor stimulation improves cognitive function and decreases cortisol secretion in depressed patients and healthy individuals","volume":"40","author":"Otte","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1210\/en.2007-0733","article-title":"Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells","volume":"149","author":"Johansson","year":"2008","journal-title":"Endocrinology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3239","DOI":"10.1210\/EN.2015-1098","article-title":"GH-releasing hormone promotes survival and prevents TNF-alpha-induced apoptosis and atrophy in C2C12 myotubes","volume":"156","author":"Gallo","year":"2015","journal-title":"Endocrinology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.brainres.2005.10.002","article-title":"Single exposure to social defeat increases corticotropin-releasing factor and glucocorticoid receptor mRNA expression in rat hippocampus","volume":"1067","author":"Marini","year":"2006","journal-title":"Brain Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1210\/endo-67-1-125","article-title":"Blocking the renal electrolyte effects of mineralocorticoids with an orally active steroidal spirolactone","volume":"67","author":"Kagawa","year":"1960","journal-title":"Endocrinology"},{"key":"B42","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.1523\/JNEUROSCI.12-09-03642.1992","article-title":"Adrenal hormones suppress cell division in the adult rat dentate gyrus","volume":"12","author":"Gould","year":"1992","journal-title":"J Neurosci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1161\/01.CIR.99.11.1485","article-title":"Aldosterone, not estradiol, is the physiological agonist for rapid increases in cAMP in vascular smooth muscle cells","volume":"99","author":"Christ","year":"1999","journal-title":"Circulation"},{"key":"B44","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1210\/mend.13.1.0226","article-title":"Modulation of human mineralocorticoid receptor function by protein kinase A","volume":"13","author":"Massaad","year":"1999","journal-title":"Mol Endocrinol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3389\/fnmol.2014.00046","article-title":"GSK-3beta, a pivotal kinase in Alzheimer disease","volume":"7","author":"Llorens-Martin","year":"2014","journal-title":"Front Mol Neurosci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1096\/fj.01-0577com","article-title":"Enhancement of p53 activity and inhibition of neural cell proliferation by glucocorticoid receptor activation","volume":"16","author":"Crochemore","year":"2002","journal-title":"FASEB J"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1046\/j.1460-9568.2003.02587.x","article-title":"Mineralocorticoid receptor expression and increased survival following neuronal injury","volume":"17","author":"Macleod","year":"2003","journal-title":"Eur J Neurosci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12379","article-title":"STRESS and DEPRESSION a crucial role of the mineralocorticoid receptor","author":"De Kloet","year":"2016","journal-title":"J Neuroendocrinol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1210\/endo.133.1.8391426","article-title":"Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system","volume":"133","author":"Reul","year":"1993","journal-title":"Endocrinology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"4688","DOI":"10.1073\/pnas.0606067104","article-title":"Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice","volume":"104","author":"Rozeboom","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e0142012","DOI":"10.1371\/journal.pone.0142012","article-title":"Overexpression of mineralocorticoid receptors partially prevents chronic stress-induced reductions in hippocampal memory and structural plasticity","volume":"10","author":"Kanatsou","year":"2015","journal-title":"PLoS One"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1016\/S0024-3205(03)00513-7","article-title":"The mineralocorticoid receptor agonist, fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone","volume":"73","author":"Otte","year":"2003","journal-title":"Life Sci"},{"key":"B53","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/j.psyneuen.2007.05.016","article-title":"The acute effects of a mineralocorticoid receptor (MR) agonist on nocturnal hypothalamic-adrenal-pituitary (HPA) axis activity in healthy controls","volume":"32","author":"Buckley","year":"2007","journal-title":"Psychoneuroendocrinology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1007\/s11102-012-0435-3","article-title":"The acute effect of fludrocortisone on basal and hCRH-stimulated hypothalamic \u2013 pituitary \u2013 adrenal (HPA) axis in humans","volume":"16","author":"Karamouzis","year":"2013","journal-title":"Pituitary"},{"key":"B55","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s00280-014-2496-7","article-title":"Differential regulation of bladder cancer growth by various glucocorticoids: corticosterone and prednisone inhibit cell invasion without promoting cell proliferation or reducing cisplatin cytotoxicity","volume":"74","author":"Ishiguro","year":"2014","journal-title":"Cancer Chemother Pharmacol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"74","DOI":"10.2174\/1875397301004010074","article-title":"A rapid, inexpensive high throughput screen method for neurite outgrowth","volume":"4","author":"Yeyeodu","year":"2010","journal-title":"Curr Chem Genomics"},{"key":"B57","doi-asserted-by":"publisher","first-page":"7211","DOI":"10.3892\/mmr.2015.4406","article-title":"Investigation into hippocampal nerve cell damage through the mineralocorticoid receptor in mice","volume":"12","author":"Sasaki","year":"2015","journal-title":"Mol Med Rep"},{"key":"B58","doi-asserted-by":"crossref","first-page":"8487","DOI":"10.1523\/JNEUROSCI.19-19-08487.1999","article-title":"Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS","volume":"19","author":"Palmer","year":"1999","journal-title":"J Neurosci"},{"key":"B59","doi-asserted-by":"publisher","first-page":"19204","DOI":"10.1073\/pnas.0507572102","article-title":"Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone","volume":"102","author":"Karst","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1111\/j.1460-9568.2008.06220.x","article-title":"Rapid changes in hippocampal CA1 pyramidal cell function via pre- as well as postsynaptic membrane mineralocorticoid receptors","volume":"27","author":"Olijslagers","year":"2008","journal-title":"Eur J Neurosci"},{"key":"B61","doi-asserted-by":"publisher","first-page":"23725","DOI":"10.1074\/jbc.M113.470146","article-title":"Non-receptor-tyrosine kinases integrate fast glucocorticoid signaling in hippocampal neurons","volume":"288","author":"Yang","year":"2013","journal-title":"J Biol Chem"},{"key":"B62","doi-asserted-by":"publisher","first-page":"9047","DOI":"10.1523\/JNEUROSCI.2797-06.2006","article-title":"Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer\u2019s disease","volume":"26","author":"Green","year":"2006","journal-title":"J Neurosci"},{"key":"B63","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1046\/j.1365-2826.2000.00475.x","article-title":"Chronic corticosterone administration dose-dependently modulates A beta((1-42))- and NMDA-induced neurodegeneration in rat magnocellular nucleus basalis","volume":"12","author":"Abraham","year":"2000","journal-title":"J Neuroendocrinol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1046\/j.1471-4159.1996.66051836.x","article-title":"Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons","volume":"66","author":"Goodman","year":"1996","journal-title":"J Neurochem"},{"key":"B65","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1006\/nbdi.2001.0395","article-title":"Corticotropin-releasing hormone protects neurons against insults relevant to the pathogenesis of Alzheimer\u2019s disease","volume":"8","author":"Pedersen","year":"2001","journal-title":"Neurobiol Dis"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T20:36:24Z","timestamp":1568061384000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/Article\/10.3389\/fendo.2016.00066\/abstract"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,16]]},"references-count":65,"URL":"https:\/\/doi.org\/10.3389\/fendo.2016.00066","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,16]]}}}