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Downregulation of EAAT2 results in glutamate accumulation, N-Methyl-D-Aspartate (NMDA) receptor overactivation, and neuronal injury. Crocin (Cr), a carotenoid compound extracted from saffron (\n                    <jats:italic>Crocus sativus<\/jats:italic>\n                    ), exhibits potent antioxidant and neuroprotective properties, particularly in experimental models of neurodegeneration. Forty-eight adult male rats were divided into six groups: control (saline), crocin (50\u00a0mg\/kg), scopolamine (3\u00a0mg\/kg for 7 days), scopolamine followed by memantine (M) (20\u00a0mg\/kg), scopolamine followed by crocin, and scopolamine followed by both memantine and crocin. This study aimed to evaluate the therapeutic potential of crocin, alone and in combination with memantine, in a scopolamine-induced rat model of Alzheimer\u2019s disease, with a focus on EAAT2 modulation. Scopolamine administration significantly elevated glutamate, NMDAR and p-tau levels while reducing p-Akt, GABA and EAAT2 levels, accompanied by marked hippocampal neurodegeneration. In contrast, crocin treatment, either alone or in combination with memantine, restored neurotransmitter balance, downregulated NMDAR, upregulated EAAT2, increased p-Akt expression level and reduced tau phosphorylation. Histological analysis further confirmed notable structural recovery of hippocampal neurons.\n                  <\/jats:p>","DOI":"10.1007\/s11064-026-04692-z","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T10:00:13Z","timestamp":1772704813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Crocin Mitigates Glutamate Excitotoxicity and Tau Hyperphosphorylation by Modulating EAAT2 and Akt\/Tau Pathway in a Scopolamine-induced Rat Model of Alzheimer\u2019s Disease"],"prefix":"10.1007","volume":"51","author":[{"given":"Safinaz E.","family":"El-Baga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed H.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eatemad A.","family":"Awadalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abd El-Kader M.","family":"Abd El-Kader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"4692_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.11.009","author":"L Vermunt","year":"2019","unstructured":"Vermunt L, Sikkes SAM, van den Hout A et al (2019) Duration of preclinical, prodromal, and dementia stages of Alzheimer\u2019s disease in relation to age, sex, and APOE genotype. 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