{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:41:07Z","timestamp":1781502067586,"version":"3.54.1"},"reference-count":5,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K06464"],"award-info":[{"award-number":["JP22K06464"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuromol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tauopathies, including Alzheimer\u2019s disease (AD), are neurodegenerative diseases characterized by abnormal tau aggregation in neurons and glial cells. Various tauopathy mouse models have been developed, including PS19, a tau-overexpressing transgenic mouse model with the P301S mutation, in which glial activation has been reported prior to the accumulation of tau. In this mouse model, tau pathology was improved by the administration of the immunosuppressant FKB506, suggesting that inflammatory responses promote the progression of tau pathology. Our previous studies have shown that the inhibition of Collapsin response mediator protein 2 (CRMP2) phosphorylation suppresses inflammation and ameliorates pathological progression in spinal cord injury and MPTP-induced Parkinson\u2019s disease models using CRMP2KI\/KI mice, in which the phosphorylation site Ser522 was replaced with Ala. Therefore, we compared glial cell activation in male PS19 and PS19; CRMP2KI\/KI mice using morphometric analysis at 5\u00a0months of age, before the onset of tau pathology. We found that the morphological changes caused by the activation of microglia and astrocytes were normalized by suppressing CRMP2 phosphorylation compared with those in PS19 mice. Cox-2 expression in hippocampal neurons was increased in PS19 mice, but this increase was suppressed in PS19; CRMP2KI\/KI mice, suggesting that the suppression of CRMP2 phosphorylation in neurons is also involved in this process. These results suggest that the inhibition of CRMP2 phosphorylation may improve neuroinflammation in tauopathy.<\/jats:p>","DOI":"10.1007\/s12017-025-08891-9","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:02:59Z","timestamp":1760414579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Suppression of Glial Activation in Tau Transgenic Mice Through Inhibition of CRMP2 Phosphorylation: a Morphometric Analysis"],"prefix":"10.1007","volume":"27","author":[{"given":"Wanying","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria Ayala","family":"Guevara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Goshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi C.","family":"Saido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Ohshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"issue":"3","key":"8891_CR1","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1111\/j.1471-4159.2007.04829.x","volume":"103","author":"AR Cole","year":"2007","unstructured":"Cole, A. R., Noble, W., van Aalten, L., Plattner, F., Meimaridou, R., Hogan, D., Taylor, M., LaFrancois, J., Gunn-Moore, F., Verkhratsky, A., Oddo, S., LaFerla, F., Giese, K. P., Dineley, K. T., Duff, K., Richardson, J. C., Yan, S. D., Hanger, D. P., Allan, S. M., & Sutherland, C. (2007). Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer\u2019s disease progression. Journal of Neurochemistry, 103(3), 1132\u20131144.","journal-title":"Journal of Neurochemistry"},{"issue":"5","key":"8891_CR2","doi-asserted-by":"publisher","first-page":"676","DOI":"10.3390\/biom15050676","volume":"15","author":"J McGroarty","year":"2025","unstructured":"McGroarty, J., Salinas, S., Evans, H., Jimenez, B., Tran, V., Kadavakollu, S., Vashist, A., & Atluri, V. (2025). Inflammasome-mediated neuroinflammation: A key driver in Alzheimer\u2019s disease pathogenesis. Biomolecules, 15(5), 676.","journal-title":"Biomolecules"},{"key":"8891_CR3","doi-asserted-by":"publisher","first-page":"7413","DOI":"10.1007\/s12035-025-04721-y","volume":"62","author":"D Noguchi","year":"2025","unstructured":"Noguchi, D., Watamura, N., Nikkuni, M., et al. (2025). Involvement of CRMP2 phosphorylation in amyloid beta-induced tau phosphorylation of hippocampal neurons in Alzheimer\u2019s disease mouse model. Molecular Neurobiology, 62, 7413\u20137420.","journal-title":"Molecular Neurobiology"},{"issue":"no. 5","key":"8891_CR4","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.14336\/AD.2022.0130-1","volume":"13","author":"QQ Tao","year":"2022","unstructured":"Tao, Q. Q., Lin, R. R., Chen, Y. H., & Wu, Z. Y. (2022). Discerning the role of blood brain barrier dysfunction in Alzheimer\u2019s disease. Aging Disease, 13(5), 1391\u20131404.","journal-title":"Aging Disease"},{"issue":"3","key":"8891_CR5","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","volume":"53","author":"Y Yoshiyama","year":"2007","unstructured":"Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V.M.-Y. (2007). Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron, 53(3), 337\u2013351.","journal-title":"Neuron"}],"container-title":["NeuroMolecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12017-025-08891-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12017-025-08891-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12017-025-08891-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:41:26Z","timestamp":1767192086000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12017-025-08891-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":5,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8891"],"URL":"https:\/\/doi.org\/10.1007\/s12017-025-08891-9","relation":{},"ISSN":["1559-1174"],"issn-type":[{"value":"1559-1174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"8 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"70"}}