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This study investigated whether maternal hyperglycemia induces persistent molecular and behavioral alterations in aged male offspring and whether maternal palmitoleic acid supplementation exerts protective effects. Methods: The pregnant rats were divided into four groups: PCM, PDM, PDM\/CPA, and PDM\/TPA. Male offspring were analyzed at 48 weeks of age. Results: Maternal hyperglycemia significantly increased cerebral RAGE expression (~1.6-fold) and tau phosphorylation (~1.8-fold), accompanied by reduced Akt phosphorylation, impaired Nrf2-related antioxidant responses, and increased inflammatory gene expression. These molecular alterations are associated with impaired recognition memory, as reflected by a marked reduction in the discrimination index in the novel object recognition test. Maternal CPA\/TPA supplementation partially attenuated these abnormalities. Conclusions: These findings suggest that maternal hyperglycemia may induce long-lasting molecular alterations associated with neuroinflammation, impaired insulin-related signaling, and cognitive dysfunction in aged offspring. Maternal palmitoleic acid supplementation may partially mitigate the adverse developmental alterations associated with intrauterine hyperglycemic exposure.<\/jats:p>","DOI":"10.3390\/nu18111748","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:06:56Z","timestamp":1780049216000},"page":"1748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal palmitoleic acid supplementation attenuates neurodegenerative programming in aged offspring exposed to gestational diabetes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4357-2772","authenticated-orcid":false,"given":"Ritsuko","family":"Kawaharada","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, Takasaki University Graduate School of Health and Welfare, 37-1, Nakaorui-machi, Takasaki 370-0033, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Takasaki University Graduate School of Health and Welfare, 37-1, Nakaorui-machi, Takasaki 370-0033, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reona","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Takasaki University of Health and Welfare, 37-1, Nakaorui-machi, Takasaki 370-0033, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyo","family":"Toriumi","sequence":"additional","affiliation":[{"name":"Department of Public Health, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3156-1348","authenticated-orcid":false,"given":"Akio","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Molecular Nutrition, Graduate School of Human Life Sciences, Jissen Women\u2019s University, 4-1-1, Osakaue, Hino 191-8510, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1007\/s10803-013-1928-2","article-title":"Maternal Diabetes and the Risk of Autism Spectrum Disorders in the Offspring: A Systematic Review and Meta-Analysis","volume":"44","author":"Xu","year":"2014","journal-title":"J. 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