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In AD-associated neuroinflammation, astrocytes play a key role, finding glial activation both in patients and in animal models. The endocannabinoid system (ECS) is a neurolipid signaling system with anti-inflammatory and neuroprotective properties implicated in AD. Astrocytes respond to external cannabinoid signals and also have their own cannabinoid signaling. Our main objective is to describe the cannabinoid signaling machinery present in hippocampal astrocytes from 3\u00d7Tg-AD mice to determine if they are actively involved in the neurodegenerative process. Primary cultures of astrocytes from the hippocampus of 3\u00d7Tg-AD and non-Tg offspring were carried out. We analyzed the gene expression of astrogliosis markers, the main components of the ECS and Ca2+ signaling. 3\u00d7Tg-AD hippocampal astrocytes show low inflammatory activity (Il1b, Il6, and Gls) and Ca2+ flow (P2rx5 and Mcu), associated with low cannabinoid signaling (Cnr1 and Cnr2). These results were more evident in females. Our study corroborates glial involvement in AD pathology, in which cannabinoid signaling plays an important role. 3\u00d7Tg-AD mice born with hippocampal astrocytes with differential gene expression of the ECS associated with an innate attenuation of their activity. In addition, we show that there are sex differences from birth in this AD animal, which should be considered when investigating the pathogenesis of the disease.<\/jats:p>","DOI":"10.3390\/ijms241612598","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T10:08:59Z","timestamp":1691575739000},"page":"12598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer\u2019s Disease: Implications for Controlling Astroglial Activity"],"prefix":"10.3390","volume":"24","author":[{"given":"Beatriz","family":"Pacheco-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Tovar","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Ben Rabaa","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Molecular Biotechnology, FH Campus Wien, University for Applied Sciences, Favoritenstra\u00dfe 222, 1100 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"S\u00e1nchez-Salido","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Vargas","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-9802","authenticated-orcid":false,"given":"Juan","family":"Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de M\u00e1laga, 29010 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\/0000-0002-4516-5795","authenticated-orcid":false,"given":"Fernando","family":"Rodr\u00edguez de Fonseca","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0478-6667","authenticated-orcid":false,"given":"Patricia","family":"Rivera","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The Cellular Phase of Alzheimer\u2019s Disease","volume":"164","author":"Karran","year":"2016","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jneuroim.2006.11.017","article-title":"Inflammatory Processes in Alzheimer\u2019s Disease","volume":"184","author":"Heneka","year":"2007","journal-title":"J. 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