{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:31:05Z","timestamp":1789047065044,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Post\u2010traumatic stress disorder (PTSD) is a psychiatric disorder characterized by anxiety, abnormal stress responses, and pathological memory formation. Research indicates that hypoxia\u2010inducible pathways might influence the neurobiology of PTSD. However, the specific relationship between hypoxia\u2010inducible factors (HIFs), neuropeptides, and brain regions remains unclear. This study investigated behavioral and molecular alterations in a rat model of PTSD, with a particular focus on the expression of HIF\u20101\u03b1, HIF\u20102\u03b1, HIF\u20103\u03b1, PACAP, and PAI\u20101 in the hippocampus and medial prefrontal cortex (mPFC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PTSD was modelled in adult male rats using the single prolonged stress (SPS) protocol, consisting of 2\u2010h immobilization, 15\u2010min forced swimming, and diethyl ether anesthesia. Behavioral assessment was performed 7 days post\u2010SPS using the open field test, elevated plus maze (EPM), and dark\u2010light box. Gene expression in the hippocampus and mPFC was quantified by RT\u2010qPCR using the 2\n                      <jats:sup>(\u2212\u0394\u0394Ct)<\/jats:sup>\n                      method with \u03b2\u2010actin as a reference gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SPS\u2010exposed rats exhibited significant anxiety\u2010like behavior. In the elevated plus maze, they showed increased freezing time (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0001), more freezing episodes (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.002), fewer open\u2010arm head dips (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.002), reduced open\u2010arm time (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.027), and shorter total distance travelled (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.026) compared to controls, whereas the reduction in open\u2010arm entries did not reach significance (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.051). In the dark\u2010light box, PTSD animals made significantly fewer entries into the light zone (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.009). No significant differences were detected in the open field test. At the molecular level, hippocampal HIF\u20101\u03b1 and HIF\u20102\u03b1 mRNA expression was significantly elevated in PTSD animals relative to controls (2.05\u2010 and 2.18\u2010fold, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). No significant changes were detected for HIF\u20103\u03b1, PACAP, or PAI\u20101 in either brain region. No significant differences in gene expression were found in the mPFC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PTSD is associated with selective upregulation of HIF\u20101\u03b1 and HIF\u20102\u03b1 in the hippocampus, suggesting region\u2010specific activation of hypoxia\u2010inducible signaling pathways in the context of traumatic stress.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71654","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T07:32:12Z","timestamp":1785915132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HIF\u20101\u03b1 and HIF\u20102\u03b1 Are Upregulated in the Hippocampus but Not in the Medial Prefrontal Cortex in Experimental PTSD"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5457-7195","authenticated-orcid":false,"given":"Denys","family":"Porkhalo","sequence":"first","affiliation":[{"name":"Department of General and Molecular Pathophysiology Bogomoletz Institute of Physiology of NAS of Ukraine  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Pashevin","sequence":"additional","affiliation":[{"name":"Department of General and Molecular Pathophysiology Bogomoletz Institute of Physiology of NAS of Ukraine  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Naumenko","sequence":"additional","affiliation":[{"name":"Department of Biophysics of Sensory Signalling Bogomoletz Institute of Physiology of NAS of Ukraine  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Dosenko","sequence":"additional","affiliation":[{"name":"Department of General and Molecular Pathophysiology Bogomoletz Institute of Physiology of NAS of Ukraine  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h6161"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010021\u201001024\u20101"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014\u20102999(03)01274\u20103"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010020\u201000988\u2010w"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201006832\u20106"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010020\u201000929\u20109"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/REVNEURO.2008.19.6.395"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1259473"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathophys.2012.06.002"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/mr\u20102022\u20100012"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.857293"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/20008066.2024.2335793"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02\u20100963fje"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11060723"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/584758"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2018.00196"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185664"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054496"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159\u00d716666180110130253"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.91"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137560"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09856"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06905"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3791\/52434"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0260\u201022.2022"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1408"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2024.1495598"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2011.05904.x"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.44"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2024.09.005"}],"container-title":["Brain 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