{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:04:58Z","timestamp":1780549498046,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Biology","award":["531-D080-D248-25"],"award-info":[{"award-number":["531-D080-D248-25"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is characterized by impaired neurotrophic support, oxidative stress, and metabolic dysfunction. Using the intracerebroventricular streptozotocin (ICV-STZ) rat model of sporadic AD, we investigated whether vitamin D3 (VitD3) and dimethyl fumarate (DMF), administered alone or in combination, modulate hippocampal neurotrophin-related signaling and redox balance. Animals were assigned to SHAM, STZ, VITD, DMF, and COMBO groups, representing control, ICV-STZ, VitD3-treated ICV-STZ, DMF-treated ICV-STZ, and combined VitD3 + DMF-treated ICV-STZ animals, respectively. Hippocampal neurotrophin processing (proBDNF and mature BDNF), downstream signaling (Akt and pAkt), IGF-1 content, mitochondrial oxoglutarate dehydrogenase (OGDH) content, citrate synthase (CS) activity, and glutathione peroxidase (GPx) activity were assessed. STZ administration showed a trend toward reduced mature BDNF content compared with the SHAM group (p = 0.07), whereas combined VitD3 and DMF treatment significantly increased mature BDNF content compared with the STZ group. The mature BDNF\/proBDNF ratio was reduced in the STZ group compared with the SHAM group and tended to be higher in the COMBO group compared with the STZ group (p = 0.09). proBDNF content remained unchanged. IGF-1, pTrkB, total Akt, and pAkt content did not differ significantly between groups. The pAkt\/Akt ratio showed a trend toward reduction in the STZ group compared with SHAM group (p = 0.09). GPx activity increased in the STZ group, while CS activity and OGDH content were not significantly altered. These findings indicate that STZ-induced neurodegeneration is characterized by redox-associated uncoupling of neurotrophic signaling rather than mitochondrial disruption. Combined VitD3 and DMF treatment partially modulated neurotrophic signaling, supporting a limited but measurable neuroprotective effect.<\/jats:p>","DOI":"10.3390\/ijms27114940","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin D3 and Dimethyl Fumarate Partially Restore Neurotrophic Signaling Without Altering Mitochondrial Integrity in the STZ-Induced Model of Sporadic AD"],"prefix":"10.3390","volume":"27","author":[{"given":"Natalia","family":"Piekarczyk","sequence":"first","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, 80-309 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Berezka","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, 80-309 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalina","family":"Domkowicz","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, 80-309 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"My\u015bli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, 80-309 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6370-2160","authenticated-orcid":false,"given":"Jan Jacek","family":"Kaczor","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, 80-309 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S317","DOI":"10.3233\/JAD-240069","article-title":"Conquering Insulin Network Dysfunctions in Alzheimer\u2019s Disease: Where Are We Today?","volume":"101","year":"2024","journal-title":"J. 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