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Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg\/kg\/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on <jats:sup>18<\/jats:sup>F-fluoro-deoxyglucose (<jats:sup>18<\/jats:sup>FDG) uptake by positron emission tomography (PET).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased <jats:sup>18<\/jats:sup>FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-\u03b1 mRNA expression found in the AD model. Increased cortical \u03b2-amyloid (A\u03b2) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced A\u03b2 transport across choroid plexus cells <jats:italic>in vitro<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased A\u03b2 clearance.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1742-2094-9-8","type":"journal-article","created":{"date-parts":[[2012,1,17]],"date-time":"2012-01-17T02:29:14Z","timestamp":1326767354000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":228,"title":["Prolonged oral cannabinoid administration prevents neuroinflammation, lowers \u03b2-amyloid levels and improves cognitive performance in Tg APP 2576 mice"],"prefix":"10.1186","volume":"9","author":[{"given":"Ana Mar\u00eda","family":"Mart\u00edn-Moreno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Brera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Spuch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Carro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A","family":"Pozo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia G","family":"Innamorato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cuadrado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda L","family":"de Ceballos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,1,16]]},"reference":[{"key":"511_CR1_511","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S0197-4580(00)00124-X","volume":"21","author":"H Akiyama","year":"2000","unstructured":"Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Giffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O'Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T: Inflammation and Alzheimer's disease. \n                           Neurobiol Aging 2000, 21:383\u2013421.","journal-title":"Neurobiol Aging"},{"key":"511_CR2_511","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/S0896-6273(02)00794-8","volume":"35","author":"T Wyss-Coray","year":"2002","unstructured":"Wyss-Coray T, Mucke L: Inflammation in neurodegenerative disease -a double-edged sword. \n                           Neuron 2002, 35:419\u2013432.","journal-title":"Neuron"},{"key":"511_CR3_511","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/0197-4580(95)00049-K","volume":"16","author":"JC Breitner","year":"1995","unstructured":"Breitner JC, Welsh KA, Helms MJ, Gaskell PC, Gau BA, Roses AD, Pericak-Vance MA, Saunders AM: Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. \n                           Neurobiol Aging 1995, 16:523\u2013530.","journal-title":"Neurobiol Aging"},{"key":"511_CR4_511","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/S0197-4580(98)00096-7","volume":"19","author":"BA In 't Veld","year":"1998","unstructured":"In 't Veld BA, Launer LJ, Hoes AW, Ott A, Hofman A, Breteler MM, Stricker BH: NSAIDs and incident Alzheimer's disease. 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