{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:13:06Z","timestamp":1789999986892,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012155","name":"National Institute for Medical Research Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004484","name":"Tehran University of Medical Sciences and Health Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004484","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012330","name":"Cognitive Sciences and Technologies Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dementia develops as a result of multiple factors, including cerebrovascular disease which is called vascular dementia (VD). Histone\u20103 lysine\u20109 dimethylation (H3K9me2) broadly increases during VD and inhibits neuroprotective gene expressions. So, we aimed to determine how H3K9me2 inhibitor (BIX01294) affects neuronal damage in VD. An in vivo model of VD was used followed by BIX01294 treatment. Behavioral tests, hematoxylin, and eosin (H&amp;E), Congo red, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were carried out. Hippocampal phosphorylated cyclic\u2010AMP responsive element binding protein (p\u2010CREB), c\u2010fos, brain\u2010derived neurotrophic factor (BDNF), and H3K9me2, were detected by western blot analysis technique. Neurological deficit and anxiety\u2010related behavior significantly reduced in the treatment group compared to the VD group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). BIX01294 improved spatial and passive avoidance memory (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05, respectively) compared to the VD group. Treatment with BIX01294 restored the level of p\u2010CREB\/CREB ratio (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), cfos (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), BDNF (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), and suppressed H3K9me2 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) when compared to the VD group. BIX01294 microinjection reduced the apoptosis level in TUNEL staining (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), and raised neural cell count in H&amp;E staining (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01); amyloid beta accumulation significantly decreased in the treatment group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) compared to the VD group. In conclusion, long\u2010term treatment with a low dose of BIX01294 can prevent the progression of neuronal loss in VD model by raising the expression of neurotrophic factors, and reducing the apoptosis level.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70001","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T04:50:37Z","timestamp":1729659037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of BIX01294 in the intracranial inhibition of H3K9 methylation lessens neuronal loss in vascular dementia model"],"prefix":"10.1002","volume":"85","author":[{"given":"Fardin","family":"Sehati","sequence":"first","affiliation":[{"name":"Department of Physiology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saereh","family":"Hosseindoost","sequence":"additional","affiliation":[{"name":"Pain Research Center, Neuroscience Institute Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Ranjbaran","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Nabavizadeh","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Tehran University of Medical Sciences Tehran Iran"},{"name":"Electrophysiology Research Center Neuroscience Institute, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed\u2010Morteza","family":"Karimian","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheila","family":"Adeli","sequence":"additional","affiliation":[{"name":"Electrophysiology Research Center Neuroscience Institute, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Zahedi","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Chodari","sequence":"additional","affiliation":[{"name":"Neurophysiology Research Center Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences Urmia Iran"},{"name":"Department of Physiology School of Medicine, Urmia University of Medical Sciences Urmia Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4853-092X","authenticated-orcid":false,"given":"Ghorbangol","family":"Ashabi","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Tehran University of Medical Sciences Tehran Iran"},{"name":"Electrophysiology Research Center Neuroscience Institute, Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2013.04.003"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.01.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623310389621"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102558"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0147-12.2012"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","unstructured":"Harman M. F. &Mart\u00edn M. G.(2019). Epigenetic mechanisms related to cognitive decline during aging.Journal of Neuroscience Research 98(2) 234\u2013246.https:\/\/doi.org\/10.1002\/jnr.24436","DOI":"10.1002\/jnr.24436"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-13-189"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.02.005"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.01.017"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113482"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1179438"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.02.012"},{"issue":"4","key":"e_1_2_10_15_1","first-page":"401","article-title":"The oxidative stress hypothesis in Alzheimer's disease","volume":"25","author":"Padurariu M.","year":"2013","journal-title":"Psychiatria Danubina"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(80)90021-7"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.21018"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000337590"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.019"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.99"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.93"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.136263"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.2478\/intox-2013-0020"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06195-2"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.1995105"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12634"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000504056"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.190"},{"issue":"18","key":"e_1_2_10_29_1","first-page":"9601","article-title":"Inflammation, apoptosis and autophagy as critical players in vascular dementia","volume":"24","author":"Wang X. X.","year":"2020","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2009.09.021"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy354"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ddr.70001","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:21:16Z","timestamp":1789996876000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,23]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/ddr.70001"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70001","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,23]]},"assertion":[{"value":"2024-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70001"}}