{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:43:43Z","timestamp":1786509823311,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R445"],"award-info":[{"award-number":["PNURSP2026R445"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder that can affect brain health, primarily through the damaging effects of prolonged hyperglycemia. This condition increases oxidative stress (OS), neuroinflammation, and neuroapoptosis, ultimately impairing cognitive function. Acrylamide (ACY), a neurotoxicant formed during high-temperature food processing and present in cigarette smoke, may further aggravate these neurological disturbances. The present experiment examined the exacerbating effects of T2DM and ACY exposure on cognitive function, neurodegeneration, OS, neuroinflammation, and neuroapoptosis in diabetic rats. T2DM was induced via intraperitoneal injections of nicotinamide and streptozotocin, followed by daily oral doses of ACY for a month. Behavioral assessments (EPM, NOR, and Y-maze) evaluated cognitive performance. Brain tissues were analyzed for biochemical markers of neurodegeneration (GSK-3\u03b2, AChE, BACE1), OS (MDA, GSH, Catalase), neuroinflammation (NF-\u03baB, TNF-\u03b1, PGE2, COX-2), and neuroapoptosis (Bcl-2, Bax, Caspase-3). Immunohistochemistry of Bcl-2, Bcl-6, CD138, and NF assessed structural brain changes. Results indicated that T2DM and ACY exposure significantly increased the incidence of neurological disturbances. Notably, through increased COX-2, PGE2, MDA, Bax, Bcl-6, Caspase-3, and cognitive decline deficits. This study highlights the harmful neurotoxic amplification of T2DM and ACY exposure, emphasizing the importance of public health measures to reduce ACY exposure through dietary and lifestyle changes, particularly among T2DM populations. Further research into neuroprotective strategies and underlying mechanisms is necessary.<\/jats:p>","DOI":"10.3390\/life16030491","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:03:27Z","timestamp":1773756207000},"page":"491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acrylamide Exposure Exacerbates Type 2 Diabetes-Induced Neurotoxicity: An Integrated Neurobehavioral and Molecular Investigation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4502-3797","authenticated-orcid":false,"given":"Abdulaziz Arif A.","family":"Alshammari","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-4315","authenticated-orcid":false,"given":"Abdullah Saleh","family":"Alkhamiss","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7255-5254","authenticated-orcid":false,"given":"Minhajul","family":"Arfeen","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9211-1042","authenticated-orcid":false,"given":"Razan","family":"Alawaji","sequence":"additional","affiliation":[{"name":"King Salman Medical City, Madina Health Cluster, Madinah 42319, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai B.","family":"Alwesmi","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Nursing, College of Nursing, Princess Nourah bint Abdulrahman University, Riyadh 11564, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8440-8366","authenticated-orcid":false,"given":"Vasudevan","family":"Mani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, March 31). 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