{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:04:34Z","timestamp":1792029874102,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Scientific Studies Fund of Bulgaria","award":["KP-06-N41\/4"],"award-info":[{"award-number":["KP-06-N41\/4"]}]},{"name":"National Scientific Studies Fund of Bulgaria","award":["BG-RRP-2.004-0002"],"award-info":[{"award-number":["BG-RRP-2.004-0002"]}]},{"name":"European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria","award":["KP-06-N41\/4"],"award-info":[{"award-number":["KP-06-N41\/4"]}]},{"name":"European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria","award":["BG-RRP-2.004-0002"],"award-info":[{"award-number":["BG-RRP-2.004-0002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The existing body of literature, in conjunction with our recent studies, shows that melatonin dysfunction can accelerate the aging process, with this effect depending on the specific age of the subject. The present study aims to ascertain the impact of pinealectomy on sphingolipid (SL) turnover in young adult (3-month-old), middle-aged (14-month-old), and old (18-month-old) rats. Ceramide (Cer) levels, neutral (NSMase) and acid sphingomyelinase (ASMase), acid ceramidase (ASAH1), and sphingosine-1-phosphate (S1P) levels in hippocampus and\/or plasma, were evaluated by enzyme-linked immunosorbent assay. The accumulation of Cer and its metabolite second messenger S1P in the hippocampus and plasma was associated with increased levels and activity of hippocampal NSMase in the hippocampus and plasma. However, no such association was observed for hippocampal ASMase, whose levels and activity were reduced in middle-aged and old rats compared to young adult rats. Pinealectomy-induced melatonin deficiency in young adult rats showed an increase in hippocampal Cer content compared to the sham group. However, in contrast to young adult rats, pinealectomy had an inverse effect on age-related changes in hippocampal Cer, NSMase, and ASMase in middle-aged rats. Furthermore, pinealectomy exacerbated the age-related increase in S1P in the hippocampus of 18-month-old rats. Collectively, the results of the present study suggest that melatonin deficiency may influence the aging process by modulating SL turnover in an age-specific manner.<\/jats:p>","DOI":"10.3390\/ijms26041694","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T03:41:47Z","timestamp":1739763707000},"page":"1694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pinealectomy-Induced Melatonin Deficiency Exerts Age-Specific Effects on Sphingolipid Turnover in Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-5099","authenticated-orcid":false,"given":"Jane","family":"Tchekalarova","sequence":"first","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 23, 1113 Sofia, Bulgaria"},{"name":"Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1458-2457","authenticated-orcid":false,"given":"Irina","family":"Georgieva","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Vukova","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Apostolova","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6659-2588","authenticated-orcid":false,"given":"Rumiana","family":"Tzoneva","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,16]]},"reference":[{"key":"ref_1","first-page":"340","article-title":"Melatonin Regulates the Aging Mouse Hippocampal Homeostasis via the Sirtuin1-FOXO1 Pathway","volume":"16","author":"Jenwitheesuk","year":"2017","journal-title":"EXCLI J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neulet.2012.09.045","article-title":"Melatonin Supplementation Delays the Decline of Adult Hippocampal Neurogenesis During Normal Aging of Mice","volume":"530","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_3","first-page":"2135","article-title":"Age-Related Decreases in Melatonin Secretion\u2014Clinical Consequences","volume":"85","author":"Wurtman","year":"2000","journal-title":"J. Clin. Endocrinol. 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