{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:24:44Z","timestamp":1780489484581,"version":"3.54.1"},"reference-count":67,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T00:00:00Z","timestamp":1659225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Stressful life events are considered major risk factors for the development of several psychiatric disorders, though people differentially cope with stress. The reasons for this are still largely unknown but could be accounted for by individual genetic variants, previous life events, or the kind of stressors. The human brain\u2010derived neurotrophic factor (BDNF) Val66Met variant, which was found to impair intracellular trafficking and activity\u2010dependent secretion of BDNF, has been associated with increased susceptibility to develop several neuropsychiatric disorders, although there is still some controversial evidence. On the other hand, acute stress has been consistently demonstrated to promote the release of glutamate in cortico\u2010limbic regions and altered glutamatergic transmission has been reported in psychiatric disorders. However, it is not known if the BDNF Val66Met single\u2010nucleotide polymorphism (SNP)\u00a0affects the stress\u2010induced presynaptic glutamate release. In this study, we exposed adult male BDNF<jats:sup>Val\/Val<\/jats:sup> and BDNF<jats:sup>Val\/Met<\/jats:sup> knock\u2010in mice to 30\u2009min of acute restraint stress. Plasma corticosterone levels, glutamate release, protein, and gene expression in the hippocampus were analyzed immediately after the end of the stress session. Acute restraint stress similarly increased plasma corticosterone levels and nuclear glucocorticoid receptor levels and phosphorylation in both BDNF<jats:sup>Val\/Val<\/jats:sup> and BDNF<jats:sup>Val\/Met<\/jats:sup> mice. However, acute restraint stress induced higher increases in hippocampal presynaptic release of glutamate, phosphorylation of cAMP\u2010response element binding protein\u00a0(CREB), and levels of the immediate early gene c\u2010fos of BDNF<jats:sup>Val\/Met<\/jats:sup> compared to BFNF<jats:sup>Val\/Val<\/jats:sup> mice. Moreover, acute restraint stress selectively increased phosphorylation levels of synapsin I at Ser<jats:sup>9<\/jats:sup> and at Ser<jats:sup>603<\/jats:sup> in BDNF<jats:sup>Val\/Val<\/jats:sup> and BDNF<jats:sup>Val\/Met<\/jats:sup> mice, respectively. In conclusion, we report\u00a0here that the BDNF Val66Met SNP knock\u2010in mice display an altered response to acute restraint stress in terms of hippocampal glutamate release, CREB phosphorylation, and neuronal activation, compared to wild\u2010type animals. Taken together, these results could partially explain the enhanced vulnerability to stressful events of Met carriers reported in both preclinical and clinical studies.<\/jats:p>","DOI":"10.1002\/jcp.30833","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T09:09:41Z","timestamp":1659258581000},"page":"3834-3844","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Acute stress induces an aberrant increase of presynaptic release of glutamate and cellular activation in the hippocampus of BDNF<sup>Val\/Met<\/sup> mice"],"prefix":"10.1002","volume":"237","author":[{"given":"Laura","family":"Musazzi","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Tornese","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze 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