{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:44:20Z","timestamp":1792395860411,"version":"4.4.0"},"reference-count":64,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Purpose<\/jats:bold>\n                    : Overtraining Syndrome (OTS) is a chronic maladaptive condition characterized by persistent performance decline due to excessive training and inadequate recovery. OTS is associated with mood disturbances, but the underlying neurobiological mechanisms remain unclear. This study investigated whether a 6\u2010week overtraining (OT) protocol induces anxiety\u2010like behavior and changes in hippocampal BBB\u2010related tight junction proteins in mice.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : Eight\u2010week\u2010old male C57BL\/6J mice were assigned to sedentary (SED,\n                    <jats:italic>n<\/jats:italic>\n                    = 5), moderate exercise (ME,\n                    <jats:italic>n<\/jats:italic>\n                    = 5), or overtraining (OT; downhill treadmill running, initially\n                    <jats:italic>n<\/jats:italic>\n                    = 10) groups and completed a 6\u2010week training protocol. The final OT sample size was\n                    <jats:italic>n<\/jats:italic>\n                    = 4 after 6 of the 10 mice were excluded due to tail or hindlimb injuries. Endurance capacity was assessed using an incremental loading test (ILT). Anxiety\u2010like behaviors were evaluated using the nest building test (NBT), open\u2010field test (OFT), and elevated plus maze (EPM). Hippocampal tight junction (TJ) proteins zonula occludens\u20101 (ZO\u20101), occludin, claudin\u20105, as well as tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) were quantified by Western blot analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : After 6 weeks, endurance performance in the OT group significantly decreased from baseline (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01) and was lower than that of the ME group at Week 6 (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.0001). In the quadriceps, TNF\u2010\u03b1 protein levels were significantly elevated in the OT group compared with both the SED (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05) and ME groups (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01). In the OFT, OT mice exhibited fewer center entries and reduced time spent in the center zone versus the SED and ME groups (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05), indicating increased anxiety related behavioral change. In the hippocampus, zonula occludens\u20101 (ZO\u20101) levels were reduced and TNF\u2010\u03b1 levels were elevated in OT compared with SED (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01 and\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05, respectively), whereas claudin\u20105 levels were higher in ME than SED (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : OT was associated with anxiety\u2010like behavioral alterations and changes in hippocampal BBB\u2010related tight junction proteins. Reduced expression of TJ proteins and increased neuroinflammation may contribute to affective symptoms observed in OTS. However, given the small final sample size in the OT group, these findings should be interpreted with caution.\n                  <\/jats:p>","DOI":"10.1002\/brb3.71709","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:22:28Z","timestamp":1788153748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Overtraining on Anxiety\u2010Like Behavior and Tight Junction Proteins of the Blood\u2013Brain Barrier in Mice"],"prefix":"10.1002","volume":"16","author":[{"given":"Eunseon","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Physical Education Seoul National University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyoung","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Physical Education Seoul National University  Seoul South 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