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Aging Neurosci."],"abstract":"<jats:p>\n                    Neuroinflammation plays an important role in the pathophysiology of Alzheimer\u2019s disease. The cannabinoid type 2 receptor (CB\n                    <jats:sub>2<\/jats:sub>\n                    R) is an emerging target for neuroinflammation and therapeutics of Alzheimer\u2019s disease. Here, we aim to assess the alterations in brain CB\n                    <jats:sub>2<\/jats:sub>\n                    R levels and evaluate novel CB\n                    <jats:sub>2<\/jats:sub>\n                    R imaging tracers in the arcA\u00df mouse model of Alzheimer\u2019s disease amyloidosis. Immunohistochemical staining for amyloid-\u00df deposits (6E10), microgliosis (anti-Iba1 and anti-CD68 antibodies), astrocytes (GFAP) and the anti-CB\n                    <jats:sub>2<\/jats:sub>\n                    R antibody was performed on brain slices from 17-month-old arcA\u00df mice. Autoradiography using the CB\n                    <jats:sub>2<\/jats:sub>\n                    R imaging probes [\n                    <jats:sup>18<\/jats:sup>\n                    F]RoSMA-18-d6, [\n                    <jats:sup>11<\/jats:sup>\n                    C]RSR-056, and [\n                    <jats:sup>11<\/jats:sup>\n                    C]RS-028 and mRNA analysis were performed in brain tissue from arcA\u00df and non-transgenic littermate (NTL) mice at 6, 17, and 24 months of age. Specific increased CB\n                    <jats:sub>2<\/jats:sub>\n                    R immunofluorescence intensities on the increased number of GFAP-positive astrocytes and Iba1-positive microglia were detected in the hippocampus and cortex of 17-month-old arcA\u00df mice compared to NTL mice. CB\n                    <jats:sub>2<\/jats:sub>\n                    R immunofluorescence was higher in glial cells inside 6E10-positive amyloid-\u00df deposits than peri-plaque glial cells, which showed low background immunofluorescence in the hippocampus and cortex of 17-month-old arcA\u00df mice.\n                    <jats:italic>Ex vivo<\/jats:italic>\n                    autoradiography showed that the specific binding of [\n                    <jats:sup>18<\/jats:sup>\n                    F]RoSMA-18-d6 and [\n                    <jats:sup>11<\/jats:sup>\n                    C]RSR-056 was comparable in arcA\u00df and NTL mice at 6, 17, and 24 months of age. The level of\n                    <jats:italic>Cnr2<\/jats:italic>\n                    mRNA expression in the brain was not significantly different between arcA\u00df and NTL mice at 6, 17, or 24 months of age. In conclusion, we demonstrated pronounced specific increases in microglial and astroglial CB\n                    <jats:sub>2<\/jats:sub>\n                    R expression levels in a mouse model of AD-related cerebral amyloidosis, emphasizing CB\n                    <jats:sub>2<\/jats:sub>\n                    R as a suitable target for imaging neuroinflammation.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2022.1018610","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T05:51:57Z","timestamp":1664517117000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Evaluation of cannabinoid type 2 receptor expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Vasil","family":"Kecheliev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Spinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"Herde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achi","family":"Haider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjing","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Klohs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M.","family":"Ametamey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqing","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1007\/s00259-016-3457-7","article-title":"Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer\u2019s disease.","volume":"43","author":"Ahmad","year":"2016","journal-title":"Eur. 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