{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:36:16Z","timestamp":1790418976515,"version":"4.1.0"},"reference-count":93,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:00:00Z","timestamp":1463443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["MH-095972"],"award-info":[{"award-number":["MH-095972"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Brain & Behavior Research Foundation National Alliance for Research on Schizophrenia and Depression (to J.J.R.)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2016,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The stress\u2010responsive hypothalamo\u2013pituitary\u2013adrenal (HPA) axis plays a central role in promoting adaptations acutely, whereas adverse effects on physiology and behavior following chronic challenges may result from overactivity of this system. Elevations in glucocorticoids, the end\u2010products of HPA activation, play roles in adaptive and maladaptive processes by targeting cognate receptors throughout neurons in limbic cortical networks to alter synaptic functioning. Because previous work has shown that chronic stress leads to functionally relevant regressive alterations in dendritic spine shape and number in pyramidal neurons in the medial prefrontal cortex (mPFC), this study examines the capacity of sustained increases in circulating corticosterone (B) alone to alter dendritic spine morphology and density in this region. Subcutaneous B pellets were implanted in rats to provide continuous exposure to levels approximating the circadian mean or peak of the steroid for 1, 2, or 3 weeks. Pyramidal neurons in the prelimbic area of the mPFC were selected for intracellular fluorescent dye filling, followed by high\u2010resolution three\u2010dimensional imaging and analysis of dendritic arborization and spine morphometry. Two or more weeks of B exposure decreased dendritic spine volume in the mPFC, whereas higher dose exposure of the steroid resulted in apical dendritic retraction and spine loss in the same cell population, with thin spine subtypes showing the greatest degree of attrition. Finally, these structural alterations were noted to persist following a 3\u2010week washout period and corresponding restoration of circadian HPA rhythmicity. These studies suggest that prolonged disruptions in adrenocortical functioning may be sufficient to induce enduring regressive structural and functional alterations in the mPFC. J. Comp. Neurol. 524:3729\u20133746, 2016. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/cne.24027","type":"journal-article","created":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T01:45:10Z","timestamp":1461721510000},"page":"3729-3746","source":"Crossref","is-referenced-by-count":60,"title":["Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex"],"prefix":"10.1002","volume":"524","author":[{"given":"Rachel M.","family":"Anderson","sequence":"first","affiliation":[{"name":"Department of Psychological and Brain Sciences and Program in Neuroscience University of Iowa Iowa City Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"Glanz","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences and Program in Neuroscience University of Iowa Iowa City Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane B.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences and Program in Neuroscience University of Iowa Iowa City Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences and Program in Neuroscience University of Iowa Iowa City Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara A.","family":"Romig\u2010Martin","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences and Program in Neuroscience University of Iowa Iowa City Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason J.","family":"Radley","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences and Program in Neuroscience University of Iowa Iowa City Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20566"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-1101"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1385-14.2014"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-7-4-351"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2010.05.003"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2015.05.001"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0759-10.2010"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0839-11.2011"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2007.04.009"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1598-05.2005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhl108"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20025"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12564"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1171203"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-09-03839.1993"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6410-09.2010"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.389"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5718-11.2012"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000122974"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2011.01.002"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20738"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.neurobiolaging.2011.06.011","article-title":"Aging impairs the control of prefrontal cortex on the release of corticosterone in response to stress and on memory consolidation","volume":"33","author":"Garrido P","year":"2012","journal-title":"Neurobiol Aging"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2138-12.2013"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.09.047"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908563106"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2014.10.008"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.09-08-02982.1989"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.1995.tb00784.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhr229"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2008.11.005"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.003"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-15-0078"},{"key":"e_1_2_7_34_1","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1523\/JNEUROSCI.10-10-03247.1990","article-title":"Hypothalamic\u2013pituitary\u2013adrenal activity in aged, cognitively impaired, and cognitively unimpaired rats","volume":"10","author":"Issa AM","year":"1990","journal-title":"J Neurosci"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1393"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018375108"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(03)00162-0"},{"key":"e_1_2_7_38_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/cne.903390402","article-title":"Pyramidal neurons in layer 5 of the rat visual cortex. I. Correlation among cell morphology, intrinsic electrophysiological properties, and axon targets","volume":"339","author":"EM Kasper","year":"1994","journal-title":"J Comp Neurol"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.054"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1747"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901720408"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-8893-7_11"},{"key":"e_1_2_7_43_1","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1523\/JNEUROSCI.10-05-01407.1990","article-title":"Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex I. Establishment of cell classes","volume":"10","author":"A Larkman","year":"1990","journal-title":"J Neurosci"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/704103"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110444108"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1184-06.2006"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3387"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706679105"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-05-02893.1994"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801153380307"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.06.028"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb07088.x"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.03.024"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-8-107"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.133.1.25"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705615105"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504011102"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-04-01568.2000"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.12.020"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2009.05.009"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/46276"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0795-05.2005"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.01.006"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.07.008"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhi104"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21588"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0287-13.2013"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4961-14.2015"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.313"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001997"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2009.07.021"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(92)90025-S"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)01287-9"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902900205"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhp003"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1636089"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00050-6"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.4161\/cib.26068"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2380-12.2012"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0512"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2032"},{"key":"e_1_2_7_82_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/cne.10628","article-title":"Quantitative morphologic classification of layer 5 neurons from mouse primary visual cortex","volume":"461","author":"A Tsiola","year":"2003","journal-title":"J Comp Neuro"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bht278"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.10279"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901950406"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06810.2002"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.08.003"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.450020410"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91597-8"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.1079"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2014.01.020"},{"key":"e_1_2_7_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08577"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0603-08.2008"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906791106"}],"container-title":["Journal of Comparative Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcne.24027","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cne.24027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T05:47:24Z","timestamp":1696571244000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cne.24027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,17]]},"references-count":93,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2016,12,15]]}},"alternative-id":["10.1002\/cne.24027"],"URL":"https:\/\/doi.org\/10.1002\/cne.24027","archive":["Portico"],"relation":{},"ISSN":["0021-9967","1096-9861"],"issn-type":[{"value":"0021-9967","type":"print"},{"value":"1096-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,17]]}}}