{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T13:35:08Z","timestamp":1793367308612,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prenatal ethanol exposure (PEE) alters fetal brain development, potentially increasing the risk of neurodegenerative diseases such as Alzheimer\u2019s disease (AD) later in life. Although glial activation is implicated in AD pathology via cannabinoid and neuroinflammatory signaling, its potential response to PEE in the developing brain and its contribution to AD pathogenesis remain unknown. Using 3\u00d7Tg-AD offspring of both sexes born to mothers with PEE, we analyzed astrogliosis, inflammatory markers, and key components of cannabinoid and Ca2+ signaling in primary cultures of hippocampal astrocytes, elements whose dysfunction contributes to neurodegeneration. Our results indicated that PEE increased astrogliosis\/inflammatory response (significant elevation of Gfap and Tnf\u03b1 expression) in hippocampal astrocytes at birth. This neuroinflammation was significantly associated with lower expression of cannabinoid receptors (Cnr1 and Gpr55), and decreased concentrations of the anti-inflammatory lipid PEA in the culture medium, probably due to a deregulated endocannabinoid enzymatic machinery (NAPE-PLD\/FAAH ratio). This research provides insights into GRP55\/PEA-mediated signaling as a potential hippocampal astrocytic mechanism influenced by maternal ethanol exposure, which may contribute to neurobiological changes associated with increased vulnerability to AD-related pathology.<\/jats:p>","DOI":"10.3390\/ijms262211154","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T16:49:51Z","timestamp":1763484591000},"page":"11154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Perinatal Ethanol Exposure Induces Astrogliosis and Decreases GRP55\/PEA-Mediated Neuroprotection in Hippocampal Astrocytes of the 3\u00d7Tg Alzheimer\u2019s Animal Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5276-6082","authenticated-orcid":false,"given":"Miguel","family":"Rodr\u00edguez-Pozo","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina\u2014IBIMA Plataforma BIONAND, 29590 M\u00e1laga, Spain"},{"name":"Departamento de Anatom\u00eda Humana, Medicina Legal e Historia de la Ciencia, Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3058-0635","authenticated-orcid":false,"given":"Beatriz","family":"Pacheco-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina\u2014IBIMA Plataforma BIONAND, 29590 M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Neurolog\u00eda, Hospital Universitario Regional de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Ben Rabaa","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en 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