{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:52:53Z","timestamp":1790477573550,"version":"4.1.0"},"reference-count":129,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre (NCN) in Poland","award":["DEC-2022\/06\/X\/NZ4\/00411"],"award-info":[{"award-number":["DEC-2022\/06\/X\/NZ4\/00411"]}]},{"name":"Statutory Activities of the Department of Animal and Human Physiology of the University of Gda\u0144sk","award":["531-D080-D248-26"],"award-info":[{"award-number":["531-D080-D248-26"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Non-motor symptoms of PD impair quality of life and remain challenging to treat. Here, we examined the effects of short- (38 days) and long-term (178 days) supplementation with the natural polyamine spermidine on anhedonia and anxiety-like behaviours in a 6-hydroxydopamine-induced rat model of PD and linked them with spermidine\u2019s anti-inflammatory properties. Behavioural assessments (cylinder, sucrose preference, elevated plus-maze tests) were conducted during progressive neurodegeneration and after oral treatment. Under the same conditions, peripheral inflammation was evaluated by the total leukocytes and their subpopulation numbers (hematological analysis) and by CD4+ and CD8+ T lymphocyte percentages (imaging flow cytometry); the plasma levels of interleukins 4 and 10 and corticosterone (enzyme-linked immunosorbent assay) were also evaluated. The safety of long-term supplementation was assessed using standard biochemical markers (chemistry analyser). Both treatment regimens reversed 6-hydroxydopamine-induced lymphopenia. Long-term spermidine treatment increased the number of TCD4+ lymphocytes and monocytes and elevated the plasma concentrations of IL-4 and IL-10, while reducing corticosterone levels. These immunomodulatory effects were associated with reduced anhedonia and anxiety. All of the biochemical safety parameters remained within normal ranges. Spermidine alleviates neuropsychiatric symptoms in a rat model of progressive neurodegeneration in the nigrostriatal system through its regulatory influence on peripheral immune responses. Exploring the systemic mechanisms underlying spermidine\u2019s effects could unveil innovative supplementation strategies and expand treatment options for managing symptoms in PD.<\/jats:p>","DOI":"10.3390\/molecules31071164","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"1164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spermidine Suppresses Peripheral Inflammation and Alleviates Non-Motor Symptoms in the 6-OHDA-Induced Rat Model of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6352-5582","authenticated-orcid":false,"given":"Beata","family":"Grembecka","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":"Oliwia","family":"Harackiewicz","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\/0000-0002-8496-5533","authenticated-orcid":false,"given":"Jan","family":"Ruci\u0144ski","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\/0000-0003-1298-4177","authenticated-orcid":false,"given":"Daria","family":"Korewo-Labelle","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3535-9684","authenticated-orcid":false,"given":"Ewelina","family":"Kurowska-Ruci\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\/0000-0001-6719-3116","authenticated-orcid":false,"given":"Irena","family":"Majkutewicz","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":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1007\/s11136-022-03187-y","article-title":"Predictors of Health-Related Quality of Life in Parkinson\u2019s Disease: The Impact of Overlap between Health-Related Quality of Life and Clinical Measures","volume":"31","author":"Ojeda","year":"2022","journal-title":"Qual. 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