{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:49:53Z","timestamp":1790383793569,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"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":["Mol Neurobiol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intracellular aggregation and accumulation of protein is a hallmark of neurodegenerative diseases. Tauopathy, which is caused by aggregated tau accumulation, is a group of neurodegenerative diseases, including frontotemporal dementia (FTD), Pick disease, and Alzheimer\u2019s disease. Similarly, synucleinopathy, which is caused by aggregated \u03b1-synuclein (\u03b1-syn) accumulation, includes Parkinson\u2019s disease and dementia with Lewy body (DLB). The interaction between tau and \u03b1-syn has been attracting attention because of similarities in symptoms and the co-existence of tau and \u03b1-syn in neural cells. Previous studies revealed that tau and \u03b1-syn promote their aggregation with each other. Additionally, other studies showed that \u03b1-syn promotes tau spreading in the mouse brain. In the present study, we investigated the relationship between tau and \u03b1-syn and the effects of their co-existence in neuronal cells on mouse pathology by double transgenic strategy. Consequently, we found increased phosphorylated tau, a declined number of neurons in the CA1 region, and increased astrocyte and microglia in the hippocampi in double transgenic mice at 8 months old. In mice that co-express tau and \u03b1-syn, locomotive activity increased and cognitive function decreased in behavioral test. These results suggest the co-existence of tau and\u03b1-syn in neurons that promote neuronal loss and impaired cognitive function in neurodegenerative conditions.<\/jats:p>","DOI":"10.1007\/s12035-025-05248-y","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T02:46:03Z","timestamp":1753411563000},"page":"15832-15843","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Co-Expression of Mutant Tau and \u03b1-Synuclein in Neurons Promotes Tau Phosphorylation, Neuronal Loss, and Neuroinflammation in Mouse Brain"],"prefix":"10.1007","volume":"62","author":[{"given":"Yuki","family":"Yamamoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Noguchi","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":[[2025,7,25]]},"reference":[{"key":"5248_CR1","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1038\/s41593-018-0235-9","volume":"21","author":"C Soto","year":"2018","unstructured":"Soto C, Pritzkow S (2018) Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases. Nat Neurosci 21:1332\u20131340. https:\/\/doi.org\/10.1038\/s41593-018-0235-9","journal-title":"Nat Neurosci"},{"key":"5248_CR2","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1002\/alz.12452","volume":"18","author":"C Sexton","year":"2022","unstructured":"Sexton C et al (2022) Current directions in tau research: highlights from Tau 2020. Alzheimer\u2019s & dementia. J Alzheimer\u2019s Association 18:988\u20131007. https:\/\/doi.org\/10.1002\/alz.12452","journal-title":"J Alzheimer's Association"},{"key":"5248_CR3","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1001\/archneur.58.2.186","volume":"58","author":"JE Galvin","year":"2001","unstructured":"Galvin JE, Lee VM, Trojanowski JQ (2001) Synucleinopathies: clinical and pathological implications. Arch Neurol. 58:186\u2013190. https:\/\/doi.org\/10.1001\/archneur.58.2.186","journal-title":"Arch Neurol."},{"key":"5248_CR4","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.neuron.2013.09.004","volume":"76","author":"JT Bendor","year":"2013","unstructured":"Bendor JT et al (2013) The function of \u03b1-synuclein. Neuron 76:1044\u201366. https:\/\/doi.org\/10.1016\/j.neuron.2013.09.004","journal-title":"Neuron"},{"key":"5248_CR5","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1093\/jnen\/62.4.389","volume":"62","author":"T Ishizawa","year":"2003","unstructured":"Ishizawa T et al (2003) Colocalization of tau and alph\u03b1-synuclein epitopes in Lewy bodies. J Neuropathol Exp Neurol 62:389\u201397. https:\/\/doi.org\/10.1093\/jnen\/62.4.389","journal-title":"J Neuropathol Exp Neurol"},{"key":"5248_CR6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3389\/fnmol.2019.00107","volume":"12","author":"E Vasili","year":"2019","unstructured":"Vasili E et al (2019) Spreading of \u03b1-synuclein and tau: a systematic comparison of the mechanisms involved. Front Mol Neurosci 12:107. https:\/\/doi.org\/10.3389\/fnmol.2019.00107","journal-title":"Front Mol Neurosci"},{"key":"5248_CR7","doi-asserted-by":"publisher","first-page":"25481","DOI":"10.1074\/jbc.274.36.25481","volume":"274","author":"PH Jensen","year":"1999","unstructured":"Jensen PH et al (1999) \u03b1-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356. J Biol Chem 274:25481\u20139. https:\/\/doi.org\/10.1074\/jbc.274.36.25481","journal-title":"J Biol Chem"},{"key":"5248_CR8","doi-asserted-by":"publisher","first-page":"2820","DOI":"10.1096\/fj.08-120410","volume":"23","author":"T Duka","year":"2009","unstructured":"Duka T et al (2009) \u03b1-synuclein contributes to GSK-3beta-catalyzed Tau phosphorylation in Parkinson\u2019s disease models. FASEB J 23:2820\u201330. https:\/\/doi.org\/10.1096\/fj.08-120410","journal-title":"FASEB J"},{"issue":"2","key":"5248_CR9","doi-asserted-by":"publisher","first-page":"e55848","DOI":"10.1371\/journal.pone.0055848","volume":"8","author":"G Ciaccioli","year":"2013","unstructured":"Ciaccioli G et al (2013) A powerful yeast model to investigate the synergistic interaction of \u03b1-synuclein and tau in neurodegeneration. PloS One 8(2):e55848. https:\/\/doi.org\/10.1371\/journal.pone.0055848","journal-title":"PloS One"},{"key":"5248_CR10","doi-asserted-by":"publisher","first-page":"4895","DOI":"10.1111\/j.1742-4658.2011.08389.x","volume":"278","author":"F Kawakami","year":"2011","unstructured":"Kawakami F et al (2011) Stimulatory effect of \u03b1-synuclein on the tau-phosphorylation by GSK-3\u03b2. FEBS J 278:4895\u2013904. https:\/\/doi.org\/10.1111\/j.1742-4658.2011.08389.x","journal-title":"FEBS J"},{"key":"5248_CR11","doi-asserted-by":"publisher","first-page":"2814","DOI":"10.1021\/acs.biochem.9b00215","volume":"58","author":"AKR Dasari","year":"2019","unstructured":"Dasari AKR et al (2019) Tau interacts with the C-terminal region of \u03b1-synuclein, promoting formation of toxic aggregates with distinct molecular conformations. Biochemistry 58:2814\u20132821. https:\/\/doi.org\/10.1021\/acs.biochem.9b00215","journal-title":"Biochemistry"},{"key":"5248_CR12","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1126\/science.1082324","volume":"300","author":"BI Giasson","year":"2003","unstructured":"Giasson BI et al (2003) Initiation and synergistic fibrillization of tau and alph\u03b1-synuclein. Science 300:636\u201340. https:\/\/doi.org\/10.1126\/science.1082324","journal-title":"Science"},{"key":"5248_CR13","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.cell.2013.05.057","volume":"154","author":"JL Guo","year":"2013","unstructured":"Guo JL et al (2013) Distinct \u03b1-synuclein strains differentially promote tau inclusions in neurons. Cell 154:103\u201317. https:\/\/doi.org\/10.1016\/j.cell.2013.05.057","journal-title":"Cell"},{"key":"5248_CR14","doi-asserted-by":"publisher","first-page":"3454","DOI":"10.1093\/brain\/awac171","volume":"145","author":"L Pan","year":"2022","unstructured":"Pan L et al (2022) Tau accelerates \u03b1-synuclein aggregation and spreading in Parkinson\u2019s disease. Brain 145:3454\u20133471. https:\/\/doi.org\/10.1093\/brain\/awac171","journal-title":"Brain"},{"issue":"1","key":"5248_CR15","doi-asserted-by":"publisher","first-page":"e20192193","DOI":"10.1084\/jem.20192193","volume":"218","author":"F Bassil","year":"2021","unstructured":"Bassil F et al (2021) \u03b1-Synuclein modulates tau spreading in mouse brains. J Exp Med 218(1):e20192193. https:\/\/doi.org\/10.1084\/jem.20192193","journal-title":"J Exp Med"},{"key":"5248_CR16","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s00415-003-1074-4","volume":"250","author":"A Lossos","year":"2003","unstructured":"Lossos A et al (2003) Frontotemporal dementia and parkinsonism with the P301S tau gene mutation in a Jewish family. J Neurol 250:733\u201340. https:\/\/doi.org\/10.1007\/s00415-003-1074-4","journal-title":"J Neurol"},{"key":"5248_CR17","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1002\/mds.20539","volume":"20","author":"M Goedert","year":"2005","unstructured":"Goedert M (2005) Tau gene mutations and their effects. Movement Disorders 20:S45-52. https:\/\/doi.org\/10.1002\/mds.20539","journal-title":"Movement Disorders"},{"key":"5248_CR18","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 et al (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337\u201351. https:\/\/doi.org\/10.1016\/j.neuron.2007.01.010","journal-title":"Neuron"},{"key":"5248_CR19","doi-asserted-by":"publisher","first-page":"6770","DOI":"10.1038\/s41598-022-10789-6","volume":"12","author":"T Ohgita","year":"2022","unstructured":"Ohgita T et al (2022) Mechanisms of enhanced aggregation and fibril formation of Parkinson\u2019s disease-related variants of \u03b1-synuclein. Sci Rep 12:6770. https:\/\/doi.org\/10.1038\/s41598-022-10789-6","journal-title":"Sci Rep"},{"key":"5248_CR20","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.1007\/s11064-022-03626-9","volume":"47","author":"A Yazawa","year":"2022","unstructured":"Yazawa A et al (2022) Effects of lanthionine ketimine-5-ethyl ester on the \u03b1-synucleinopathy mouse model. Neurochem Res 47:2373\u20132382. https:\/\/doi.org\/10.1007\/s11064-022-03626-9","journal-title":"Neurochem Res"},{"key":"5248_CR21","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","volume":"9","author":"HS Kwon","year":"2020","unstructured":"Kwon HS, Seong-Ho K (2020) Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener 9:42. https:\/\/doi.org\/10.1186\/s40035-020-00221-2","journal-title":"Transl Neurodegener"},{"key":"5248_CR22","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, Lennart M (2002) Inflammation in neurodegenerative disease\u2013a double-edged sword. Neuron 35:419\u201332. https:\/\/doi.org\/10.1016\/s0896-6273(02)00794-8","journal-title":"Neuron"},{"key":"5248_CR23","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1126\/science.aaf6260","volume":"353","author":"MV Russo","year":"2016","unstructured":"Russo MV, McGavern DB (2016) Inflammatory neuroprotection following traumatic brain injury. Science 353:783\u20135. https:\/\/doi.org\/10.1126\/science.aaf6260","journal-title":"Science"},{"key":"5248_CR24","first-page":"1003","volume":"1","author":"D Kempuraj","year":"2016","unstructured":"Kempuraj D et al (2016) Neuroinflammation induces neurodegeneration. J Neurol Neurosurg Spine 1:1003","journal-title":"J Neurol Neurosurg Spine"},{"key":"5248_CR25","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.expneurol.2018.08.007","volume":"310","author":"JR Perea","year":"2018","unstructured":"Perea JR et al (2018) Dephosphorylated rather than hyperphosphorylated Tau triggers a pro-inflammatory profile in microglia through the p38 MAPK pathway. Exp Neurol 310:14\u201321. https:\/\/doi.org\/10.1016\/j.expneurol.2018.08.007","journal-title":"Exp Neurol"},{"key":"5248_CR26","doi-asserted-by":"publisher","unstructured":"Daniele SG et al (2015) Activation of MyD88-dependent TLR1\/2 signaling by misfolded \u03b1-synuclein, a protein linked to neurodegenerative disorders.\u00a0Sci Signal 8:376.ra45. https:\/\/doi.org\/10.1126\/scisignal.2005965","DOI":"10.1126\/scisignal.2005965"},{"key":"5248_CR27","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s00011-022-01676-x","volume":"72","author":"L Qian-Kun","year":"2023","unstructured":"Qian-Kun L et al (2023) Role of \u03b1-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson\u2019s disease. Inflamm Res 72:443\u2013462. https:\/\/doi.org\/10.1007\/s00011-022-01676-x","journal-title":"Inflamm Res"},{"key":"5248_CR28","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s41467-020-20322-w","volume":"12","author":"P Wang","year":"2021","unstructured":"Wang P, Yihong Y (2021) Filamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex. Nat Comm 12:95. https:\/\/doi.org\/10.1038\/s41467-020-20322-w","journal-title":"Nat Comm"},{"key":"5248_CR29","doi-asserted-by":"publisher","first-page":"9262","DOI":"10.1074\/jbc.M109.081125","volume":"285","author":"HJ Lee","year":"2010","unstructured":"Lee HJ et al (2010) Direct transfer of alph\u03b1-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 285:9262\u201372. https:\/\/doi.org\/10.1074\/jbc.M109.081125","journal-title":"J Biol Chem"},{"key":"5248_CR30","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3390\/neurosci5010005","volume":"5","author":"D Brash-Arias","year":"2024","unstructured":"Brash-Arias D et al (2024) The role of astrocytes and alph\u03b1-synuclein in Parkinson\u2019s disease: a review. NeuroSci 5:71\u201386. https:\/\/doi.org\/10.3390\/neurosci5010005","journal-title":"NeuroSci"},{"key":"5248_CR31","doi-asserted-by":"publisher","first-page":"7281","DOI":"10.1523\/JNEUROSCI.0490-10.2010","volume":"30","author":"LK Clinton","year":"2010","unstructured":"Clinton LK et al (2010) Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. J Neurosci 30:7281\u20139. https:\/\/doi.org\/10.1523\/JNEUROSCI.0490-10.2010","journal-title":"J Neurosci"},{"key":"5248_CR32","doi-asserted-by":"publisher","first-page":"8968","DOI":"10.1073\/pnas.132197599","volume":"99","author":"MK Lee","year":"2002","unstructured":"Lee MK et al (2002) Human alph\u03b1-synuclein-harboring familial Parkinson\u2019s disease-linked Ala-53 \u2013> Thr mutation causes neurodegenerative disease with alph\u03b1-synuclein aggregation in transgenic mice. PNAS 99:8968\u201373. https:\/\/doi.org\/10.1073\/pnas.132197599","journal-title":"PNAS"},{"key":"5248_CR33","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1007\/s11064-022-03642-9","volume":"47","author":"M Takahashi","year":"2022","unstructured":"Takahashi M et al (2022) Valproic acid-induced anxiety and depression behaviors are ameliorated in p39 Cdk5 activator-deficient mice. Neurochem Res 47:2773\u20132779. https:\/\/doi.org\/10.1007\/s11064-022-03642-9","journal-title":"Neurochem Res"},{"key":"5248_CR34","doi-asserted-by":"publisher","first-page":"e21050","DOI":"10.1371\/journal.pone.0021050","volume":"6","author":"H Takeuchi","year":"2011","unstructured":"Takeuchi H et al (2011) P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating. PloS One 6:e21050. https:\/\/doi.org\/10.1371\/journal.pone.0021050","journal-title":"PloS One"},{"key":"5248_CR35","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.neuron.2019.10.010","volume":"105","author":"F Bassil","year":"2020","unstructured":"Bassil F et al (2020) Amyloid-beta (A\u03b2) plaques promote seeding and spreading of alpha-synuclein and tau in a mouse model of Lewy body disorders with A\u03b2 pathology. Neuron 105:260-275.e6. https:\/\/doi.org\/10.1016\/j.neuron.2019.10.010","journal-title":"Neuron"},{"key":"5248_CR36","doi-asserted-by":"publisher","first-page":"eaba3239","DOI":"10.1126\/sciadv.aba3239","volume":"6","author":"EC Damisah","year":"2020","unstructured":"Damisah EC et al (2020) Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Sci Adv 6:eaba3239. https:\/\/doi.org\/10.1126\/sciadv.aba3239","journal-title":"Sci Adv"},{"key":"5248_CR37","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","volume":"8","author":"C Gao","year":"2023","unstructured":"Gao C et al (2023) Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduct Target Ther 8:359. https:\/\/doi.org\/10.1038\/s41392-023-01588-0","journal-title":"Signal Transduct Target Ther"},{"key":"5248_CR38","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrn2038","volume":"8","author":"M Block","year":"2007","unstructured":"Block M, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57\u201369. https:\/\/doi.org\/10.1038\/nrn2038","journal-title":"Nat Rev Neurosci"},{"key":"5248_CR39","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41586-021-03960-y","volume":"599","author":"KA Guttenplan","year":"2021","unstructured":"Guttenplan KA et al (2021) Neurotoxic reactive astrocytes induce cell death via saturated lipids. Nature 599:102\u2013107. https:\/\/doi.org\/10.1038\/s41586-021-03960-y","journal-title":"Nature"},{"key":"5248_CR40","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","volume":"541","author":"SA Liddelow","year":"2017","unstructured":"Liddelow SA et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481\u2013487. https:\/\/doi.org\/10.1038\/nature21029","journal-title":"Nature"},{"key":"5248_CR41","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.bbadis.2004.07.002","volume":"1739","author":"SC Feinstein","year":"2005","unstructured":"Feinstein SC, Wilson L (2005) Inability of tau to properly regulate neuronal microtubule dynamics: a loss-of-function mechanism by which tau might mediate neuronal cell death. Biochim Biophys Acta 1739:268\u201379. https:\/\/doi.org\/10.1016\/j.bbadis.2004.07.002","journal-title":"Biochim Biophys Acta"},{"key":"5248_CR42","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.bbadis.2004.06.018","volume":"1739","author":"R Brandt","year":"2005","unstructured":"Brandt R et al (2005) Tau alteration and neuronal degeneration in tauopathies: mechanisms and models. Biochim Biophys Acta 1739:331\u201354. https:\/\/doi.org\/10.1016\/j.bbadis.2004.06.018","journal-title":"Biochim Biophys Acta"},{"key":"5248_CR43","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.neuron.2016.12.023","volume":"93","author":"H Fu","year":"2017","unstructured":"Fu H et al (2017) Tau pathology induces excitatory neuron loss, grid cell dysfunction, and spatial memory deficits reminiscent of early Alzheimer\u2019s disease. Neuron. 93:533-541.e5. https:\/\/doi.org\/10.1016\/j.neuron.2016.12.023","journal-title":"Neuron."},{"key":"5248_CR44","doi-asserted-by":"publisher","first-page":"599","DOI":"10.2353\/ajpath.2006.060002","volume":"169","author":"K Schindowski","year":"2006","unstructured":"Schindowski K et al (2006) Alzheimer\u2019s disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits. Am J Pathol. 169:599\u2013616. https:\/\/doi.org\/10.2353\/ajpath.2006.060002","journal-title":"Am J Pathol."},{"key":"5248_CR45","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.neurobiolaging.2021.09.006","volume":"109","author":"H Patel","year":"2022","unstructured":"Patel H et al (2022) Pathological tau and reactive astrogliosis are associated with distinct functional deficits in a mouse model of tauopathy. Neurobiol Aging. 109:52\u201363. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2021.09.006","journal-title":"Neurobiol Aging."},{"key":"5248_CR46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI161987","volume":"133","author":"D Dutta","year":"2023","unstructured":"Dutta D et al (2023) Tau fibrils induce glial inflammation and neuropathology via TLR2 in Alzheimer\u2019s disease-related mouse models. J Clin Invest. 133:e161987. https:\/\/doi.org\/10.1172\/JCI161987","journal-title":"J Clin Invest."},{"key":"5248_CR47","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s00401-023-02547-3","volume":"145","author":"C Nanclares","year":"2023","unstructured":"Nanclares C et al (2023) Dysregulation of astrocytic Ca2+ signaling and gliotransmitter release in mouse models of \u03b1-synucleinopathies. Acta Neuropathol. 145:597\u2013610. https:\/\/doi.org\/10.1007\/s00401-023-02547-3","journal-title":"Acta Neuropathol."},{"key":"5248_CR48","doi-asserted-by":"publisher","first-page":"5091","DOI":"10.1093\/hmg\/dds355","volume":"21","author":"M Dumont","year":"2012","unstructured":"Dumont M et al (2012) Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice. Hum Mol Genet 21:5091\u2013105. https:\/\/doi.org\/10.1093\/hmg\/dds355","journal-title":"Hum Mol Genet"},{"key":"5248_CR49","doi-asserted-by":"publisher","first-page":"4063","DOI":"10.1096\/fj.11-186650","volume":"25","author":"M Dumont","year":"2011","unstructured":"Dumont M et al (2011) Behavioral deficit, oxidative stress, and mitochondrial dysfunction precede tau pathology in P301S transgenic mice. FASEB J 25:4063\u201372. https:\/\/doi.org\/10.1096\/fj.11-186650","journal-title":"FASEB J"},{"key":"5248_CR50","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12974-020-01749-w","volume":"17","author":"Y Sun","year":"2020","unstructured":"Sun Y et al (2020) The behavioural and neuropathologic sexual dimorphism and absence of MIP-3\u03b1 in tau P301S mouse model of Alzheimer\u2019s disease. J Neuroinflammation. 17:72. https:\/\/doi.org\/10.1186\/s12974-020-01749-w","journal-title":"J Neuroinflammation."},{"key":"5248_CR51","doi-asserted-by":"publisher","first-page":"e70274","DOI":"10.1371\/journal.pone.0070274","volume":"8","author":"KL Paumier","year":"2013","unstructured":"Paumier KL et al (2013) Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson\u2019s disease. PloS One 8:e70274. https:\/\/doi.org\/10.1371\/journal.pone.0070274","journal-title":"PloS One"},{"key":"5248_CR52","unstructured":"Curzon P, Rustay NR, Browman KE (2009) Cued and contextual fear conditioning for rodents. In: Buccafusco JJ, editor. Methods of behavior analysis in neuroscience. 2nd edition. Boca Raton (FL): CRC Press\/Taylor & Francis. Chapter 2.\u00a0https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK5223\/"},{"key":"5248_CR53","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1046\/j.0953-816x.2001.01609.x","volume":"13","author":"B Sacchetti","year":"2001","unstructured":"Sacchetti B et al (2001) Long-lasting hippocampal potentiation and contextual memory consolidation. Eur J Neurosci 13:2291\u20138. https:\/\/doi.org\/10.1046\/j.0953-816x.2001.01609.x","journal-title":"Eur J Neurosci"},{"key":"5248_CR54","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1002\/hipo.23381","volume":"31","author":"M Subramaniyan","year":"2021","unstructured":"Subramaniyan M et al (2021) Fear conditioning potentiates the hippocampal CA1 commissural pathway in vivo and increases awake phase sleep. Hippocampus 31:1154\u20131175. https:\/\/doi.org\/10.1002\/hipo.23381","journal-title":"Hippocampus"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05248-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-025-05248-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05248-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T13:13:15Z","timestamp":1761570795000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-025-05248-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":54,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["5248"],"URL":"https:\/\/doi.org\/10.1007\/s12035-025-05248-y","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,25]]},"assertion":[{"value":"21 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 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":"Competing interests"}}]}}