{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:13:13Z","timestamp":1783487593869,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (\n                    <jats:sc>AD<\/jats:sc>\n                    ) initiates with subtle neuroimmune alterations that precede overt synaptic loss and neuronal death, yet the early sequence linking A\u03b2 exposure to glial activation remains incompletely understood. To capture early neuroimmune dynamics with greater physiological relevance, we employed primary mixed neuron\u2013glia cultures derived from the hippocampi of postnatal day 1 (P1) mice. Unlike conventional coculture systems, these hippocampal mixed cultures preserve intrinsic neuron\u2013astrocyte\u2013microglia communication and recapitulate key features of the in\u00a0vivo hippocampal microenvironment. Using this model, we investigated whether cannabidiol (CBD) modulates the initial pathogenic events triggered by A\u03b2\n                    <jats:sub>25\u201335<\/jats:sub>\n                    during a 24h simultaneous cotreatment in cell culture. A\u03b2 exposure induced robust hippocampal glial activation, oxidative stress, and elevated levels of proinflammatory mediators, particularly IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1. Notably, hippocampal synaptic and neurogenic markers (5HT\n                    <jats:sub>1<\/jats:sub>\n                    A, Gria1, GRIN1, DCX, PSD\u201095) remained largely unaltered at this early stage, revealing a temporal dissociation in which glial\u2010driven inflammation precedes synaptic dysfunction. CBD significantly attenuated inflammatory and oxidative responses and prevented A\u03b2\u2010induced cellular damage, indicating engagement of endocannabinoid\u2010related mechanisms that constrain early hippocampal glial reactivity. Although CBD did not fully normalize all glial alterations, it preserved hippocampal synaptic integrity and halted progression toward neuronal dysfunction. Together, these findings identify early hippocampal glial inflammation as a primary target of CBD and provide mechanistic insight into the temporal sequence linking A\u03b2 exposure to neuroimmune activation. These results highlight early glial responses as a critical window for therapeutic intervention and support cannabinoid\u2010based strategies to modulate the initial stages of Alzheimer's disease pathogenesis.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70588","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:06:52Z","timestamp":1782173212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cannabidiol Limits Early A\u03b2\u2010Induced Glial Activation and Preserves Synaptic Integrity in Primary Mouse Hippocampal Neuron\u2013Glia Cultures"],"prefix":"10.1111","volume":"63","author":[{"given":"Karen del Carmen Barboza","family":"Salgado","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology and Biomaterials Federal University of Ouro Preto  Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Luiza Sciandretti","family":"de Albuquerque","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Biomaterials Federal University of Ouro Preto  Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamiles Caroline Fernandes","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology of Inflammation Federal University of Ouro Preto  Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andressa Aparecida Batista","family":"Cota","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Biomaterials Federal University of Ouro Preto  Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6685-6229","authenticated-orcid":false,"given":"Andr\u00e9","family":"Talvani","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology of Inflammation Federal University of Ouro Preto  Ouro Preto Brazil"},{"name":"Department of Biological Science Federal University of Ouro Preto  Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laser Antonio Machado","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Biomaterials Federal University of Ouro Preto  Ouro Preto Brazil"},{"name":"Department of Biological Science Federal University of Ouro Preto  Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5495-2558","authenticated-orcid":false,"given":"Katiane de Oliveira Pinto Coelho","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Biomaterials Federal University of Ouro Preto  Ouro Preto Brazil"},{"name":"Department of Biological Science Federal University of Ouro Preto  Ouro Preto 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