{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:19:03Z","timestamp":1791433143777,"version":"4.3.3"},"reference-count":69,"publisher":"Society for Neuroscience","issue":"8","license":[{"start":{"date-parts":[[2005,8,23]],"date-time":"2005-08-23T00:00:00Z","timestamp":1124755200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2005,2,23]]},"abstract":"<jats:p>Alzheimer's disease (AD) is characterized by enhanced \u03b2-amyloid peptide (\u03b2A) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity<jats:italic>in vitro<\/jats:italic>and acute brain damage<jats:italic>in vivo<\/jats:italic>. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after \u03b2A treatment, both<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>. Here, we show that senile plaques in AD patients express cannabinoid receptors CB<jats:sub>1<\/jats:sub>and CB<jats:sub>2<\/jats:sub>, together with markers of microglial activation, and that CB<jats:sub>1<\/jats:sub>-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB<jats:sub>1<\/jats:sub>receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB<jats:sub>1<\/jats:sub>and CB<jats:sub>2<\/jats:sub>proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent \u03b2A-induced microglial activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block \u03b2A-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-\u03b1 release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB<jats:sub>2<\/jats:sub>-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after \u03b2A addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.<\/jats:p>","DOI":"10.1523\/jneurosci.4540-04.2005","type":"journal-article","created":{"date-parts":[[2005,2,23]],"date-time":"2005-02-23T22:18:03Z","timestamp":1109197083000},"page":"1904-1913","source":"Crossref","is-referenced-by-count":650,"title":["Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation"],"prefix":"10.1523","volume":"25","author":[{"given":"Bel\u00e9n G.","family":"Ram\u00edrez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bl\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa G\u00f3mez","family":"del Pulgar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Guzm\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda L.","family":"de Ceballos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2005,2,23]]},"reference":[{"key":"2023041303111313000_25.8.1904.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00124-X"},{"key":"2023041303111313000_25.8.1904.2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200004)47:4<524::AID-ANA19>3.0.CO;2-5"},{"key":"2023041303111313000_25.8.1904.3","doi-asserted-by":"publisher","DOI":"10.1038\/78682"},{"key":"2023041303111313000_25.8.1904.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9328"},{"key":"2023041303111313000_25.8.1904.5","doi-asserted-by":"crossref","first-page":"11136","DOI":"10.1523\/JNEUROSCI.23-35-11136.2003","volume":"23","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303111313000_25.8.1904.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.23.13973"},{"key":"2023041303111313000_25.8.1904.7","first-page":"1632","volume":"282","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041303111313000_25.8.1904.8","doi-asserted-by":"publisher","DOI":"10.1124\/mol.60.1.155"},{"key":"2023041303111313000_25.8.1904.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)03362-5"},{"key":"2023041303111313000_25.8.1904.10","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/nn941","volume":"5","year":"2002","journal-title":"Nat Neurosci"},{"key":"2023041303111313000_25.8.1904.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(96)00922-3"},{"key":"2023041303111313000_25.8.1904.12","first-page":"86","volume":"132","year":"1988","journal-title":"Am J Pathol"},{"key":"2023041303111313000_25.8.1904.13","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10177"},{"key":"2023041303111313000_25.8.1904.14","first-page":"443","volume":"48","year":"1995","journal-title":"Mol Pharmacol"},{"key":"2023041303111313000_25.8.1904.15","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.nbd.2003.12.006","volume":"15","year":"2004","journal-title":"Neurobiol Dis"},{"key":"2023041303111313000_25.8.1904.16","first-page":"307","volume":"152","year":"1998","journal-title":"Am J Pathol"},{"key":"2023041303111313000_25.8.1904.17","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1523\/JNEUROSCI.22-03-00782.2002","volume":"22","year":"2002","journal-title":"J Neurosci"},{"key":"2023041303111313000_25.8.1904.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00428-9"},{"key":"2023041303111313000_25.8.1904.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00008-7"},{"key":"2023041303111313000_25.8.1904.20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205797200"},{"key":"2023041303111313000_25.8.1904.21","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01536.x"},{"key":"2023041303111313000_25.8.1904.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.5.1932"},{"key":"2023041303111313000_25.8.1904.23","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0289"},{"key":"2023041303111313000_25.8.1904.24","first-page":"161","volume":"54","year":"2002","journal-title":"Classification of cannabinoid receptors. 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