{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:13:16Z","timestamp":1791414796372,"version":"4.3.3"},"reference-count":54,"publisher":"Society for Neuroscience","issue":"12","license":[{"start":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T00:00:00Z","timestamp":1348185600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2012,3,21]]},"abstract":"<jats:p>Brain-derived neurotrophic factor (BDNF) plays important roles in cell survival, neural plasticity, learning, and stress regulation. However, whether the recently found human<jats:italic>BDNF<\/jats:italic>Val66Met (<jats:italic>BDNF<\/jats:italic><jats:sub>Met<\/jats:sub>) polymorphism could alter stress vulnerability remains controversial. More importantly, the molecular and structural mechanisms underlying the interaction between the<jats:italic>BDNF<\/jats:italic><jats:sub>Met<\/jats:sub>polymorphism and stress are unclear. We found that heterozygous<jats:italic>BDNF<\/jats:italic><jats:sup>+\/Met<\/jats:sup>mice displayed hypothalamic-pituitary-adrenal axis hyperreactivity, increased depressive-like and anxiety-like behaviors, and impaired working memory compared with WT mice after 7 d restraint stress. Moreover,<jats:italic>BDNF<\/jats:italic><jats:sup>+\/Met<\/jats:sup>mice exhibited more prominent changes in BDNF levels and apical dendritic spine density in the prefrontal cortex and amygdala after stress, which correlated with the impaired working memory and elevated anxiety-like behaviors. Finally, the depressive-like behaviors in<jats:italic>BDNF<\/jats:italic><jats:sup>+\/Met<\/jats:sup>mice could be selectively rescued by acute administration of desipramine but not fluoxetine. These data indicate selective behavioral, molecular, and structural deficits resulting from the interaction between stress and the human genetic<jats:italic>BDNF<\/jats:italic><jats:sub>Met<\/jats:sub>polymorphism. Importantly, desipramine but not fluoxetine has antidepressant effects on<jats:italic>BDNF<\/jats:italic><jats:sup>+\/Met<\/jats:sup>mice, suggesting that specific classes of antidepressant may be a more effective treatment option for depressive symptoms in humans with this genetic variant BDNF.<\/jats:p>","DOI":"10.1523\/jneurosci.5048-11.2012","type":"journal-article","created":{"date-parts":[[2012,3,22]],"date-time":"2012-03-22T23:37:36Z","timestamp":1332459456000},"page":"4092-4101","source":"Crossref","is-referenced-by-count":257,"title":["Variant Brain-Derived Neurotrophic Factor Val66Met Polymorphism Alters Vulnerability to Stress and Response to Antidepressants"],"prefix":"10.1523","volume":"32","author":[{"given":"Hui","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Dong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2012,3,21]]},"reference":[{"key":"2023041303553313000_32.12.4092.1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145709000248"},{"key":"2023041303553313000_32.12.4092.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2009.12.008"},{"key":"2023041303553313000_32.12.4092.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.02.007"},{"key":"2023041303553313000_32.12.4092.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1120972"},{"key":"2023041303553313000_32.12.4092.5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301360"},{"key":"2023041303553313000_32.12.4092.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2009.05.014"},{"key":"2023041303553313000_32.12.4092.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0348-04.2004"},{"key":"2023041303553313000_32.12.4092.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129663"},{"key":"2023041303553313000_32.12.4092.9","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301570"},{"key":"2023041303553313000_32.12.4092.10","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1683"},{"key":"2023041303553313000_32.12.4092.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2009.10.009"},{"key":"2023041303553313000_32.12.4092.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-1935-3"},{"key":"2023041303553313000_32.12.4092.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.017"},{"key":"2023041303553313000_32.12.4092.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.05.047"},{"key":"2023041303553313000_32.12.4092.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.02.013"},{"key":"2023041303553313000_32.12.4092.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4530(00)00040-8"},{"key":"2023041303553313000_32.12.4092.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00035-7"},{"key":"2023041303553313000_32.12.4092.18","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2649"},{"key":"2023041303553313000_32.12.4092.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2009.01.003"},{"key":"2023041303553313000_32.12.4092.20","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.143"},{"key":"2023041303553313000_32.12.4092.21","doi-asserted-by":"publisher","DOI":"10.1002\/da.20605"},{"key":"2023041303553313000_32.12.4092.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.08.053"},{"key":"2023041303553313000_32.12.4092.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605180103"},{"key":"2023041303553313000_32.12.4092.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.04.009"},{"key":"2023041303553313000_32.12.4092.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.10.015"},{"key":"2023041303553313000_32.12.4092.26","doi-asserted-by":"publisher","DOI":"10.1046\/j.1601-1848.2003.00050.x"},{"key":"2023041303553313000_32.12.4092.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2006.02.002"},{"key":"2023041303553313000_32.12.4092.28","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(03)00162-0"},{"key":"2023041303553313000_32.12.4092.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.10.026"},{"key":"2023041303553313000_32.12.4092.30","doi-asserted-by":"publisher","DOI":"10.1159\/000258639"},{"key":"2023041303553313000_32.12.4092.31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1184-06.2006"},{"key":"2023041303553313000_32.12.4092.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.03.003"},{"key":"2023041303553313000_32.12.4092.33","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2639"},{"key":"2023041303553313000_32.12.4092.34","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20744"},{"key":"2023041303553313000_32.12.4092.35","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-052209-100430"},{"key":"2023041303553313000_32.12.4092.36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504011102"},{"key":"2023041303553313000_32.12.4092.37","doi-asserted-by":"publisher","DOI":"10.1007\/s002130051156"},{"key":"2023041303553313000_32.12.4092.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(01)00515-7"},{"key":"2023041303553313000_32.12.4092.39","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301574"},{"key":"2023041303553313000_32.12.4092.40","doi-asserted-by":"publisher","DOI":"10.1038\/266730a0"},{"key":"2023041303553313000_32.12.4092.41","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2651"},{"key":"2023041303553313000_32.12.4092.42","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.114"},{"key":"2023041303553313000_32.12.4092.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.11.015"},{"key":"2023041303553313000_32.12.4092.44","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300053"},{"key":"2023041303553313000_32.12.4092.45","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4843-06.2007"},{"key":"2023041303553313000_32.12.4092.46","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1523\/JNEUROSCI.15-03-01768.1995","article-title":"Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus","volume":"15","author":"Smith","year":"1995","journal-title":"J Neurosci"},{"key":"2023041303553313000_32.12.4092.47","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5725-10.2011"},{"key":"2023041303553313000_32.12.4092.48","doi-asserted-by":"crossref","first-page":"RC23","DOI":"10.1523\/JNEUROSCI.19-18-j0001.1999","article-title":"Activation of cAMP-dependent protein kinase A in prefrontal cortex impairs working memory performance","volume":"19","author":"Taylor","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303553313000_32.12.4092.49","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.109"},{"key":"2023041303553313000_32.12.4092.50","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2259-11.2011"},{"key":"2023041303553313000_32.12.4092.51","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30576"},{"key":"2023041303553313000_32.12.4092.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.07.055"},{"key":"2023041303553313000_32.12.4092.53","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1300"},{"key":"2023041303553313000_32.12.4092.54","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(03)00418-9"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.5048-11.2012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T21:00:04Z","timestamp":1681419604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.5048-11.2012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,21]]},"references-count":54,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2012,3,21]]},"published-print":{"date-parts":[[2012,3,21]]}},"alternative-id":["10.1523\/JNEUROSCI.5048-11.2012"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.5048-11.2012","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,21]]}}}