{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:19:29Z","timestamp":1791980369368,"version":"4.4.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T00:00:00Z","timestamp":1507766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AG042178"],"award-info":[{"award-number":["AG042178"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AG047812"],"award-info":[{"award-number":["AG047812"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NS105473"],"award-info":[{"award-number":["NS105473"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016183","name":"Garrison Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016183","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer\u2019s Association SAGA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The purpose of our study was to understand the toxic effects of hippocampal phosphorylated tau in tau mice. Using rotarod and Morris water maze (MWM) tests, immunoblotting and immunofluorescence, Golgi-Cox staining and transmission electron microscopy, we assessed cognitive behavior, measured protein levels of mitochondrial dynamics, MAP2, total and phosphorylated tau, and quantified dendritic spines and mitochondrial number and length in 12-month-old tau mice with P301L mutation. Mitochondrial function was assessed by measuring the levels of H2O2, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP. MWM and rotarod tests revealed that hippocampal learning and memory and motor learning and coordination were impaired in tau mice relative to wild-type (WT) mice. Increased levels of mitochondrial fission proteins, Drp1 and Fis1 and decreased levels of mitochondrial fusion proteins, Mfn1, Mfn2 and Opa1 were found in 12-month-old tau mice relative to age-matched WT mice, indicating that the presence of abnormal mitochondrial dynamics in tau mice. Decreased levels of dendritic protein, MAP2 and increased levels of total and phosphorylated tau proteins were found in tau mice relative to WT mice. Mitochondrial function was defective. Golgi-Cox staining analysis revealed that dendritic spines are significantly reduced. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in tau mice. These findings suggest that hippocampal accumulation of phosphorylated tau is responsible for abnormal mitochondrial dynamics and reducing dendritic protein MAP2 and dendritic spines and hippocampal based learning and memory impairments, and mitochondrial structural and functional changes in tau mice. Based on these observations, we propose that reduced hippocampal phosphorylated tau is an important therapeutic strategy for AD and other tauopathies.<\/jats:p>","DOI":"10.1093\/hmg\/ddx381","type":"journal-article","created":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T15:10:50Z","timestamp":1507734650000},"page":"30-40","source":"Crossref","is-referenced-by-count":225,"title":["Hippocampal phosphorylated tau induced cognitive decline, dendritic spine loss and mitochondrial abnormalities in a mouse model of Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"27","author":[{"given":"Ramesh","family":"Kandimalla","sequence":"first","affiliation":[{"name":"Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA"},{"name":"Neuroscience & Pharmacology Department, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Manczak","sequence":"additional","affiliation":[{"name":"Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangling","family":"Yin","sequence":"additional","affiliation":[{"name":"Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA"},{"name":"Neuroscience & Pharmacology Department, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Hemachandra","family":"Reddy","sequence":"additional","affiliation":[{"name":"Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA"},{"name":"Neuroscience & Pharmacology Department, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Cell Biology & Biochemistry Department, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Neurology Department, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Speech, Language and Hearing Sciences Departments, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Garrison Institute on Aging, Texas Tech University Health Sciences Center, South West Campus, Lubbock, TX 79413, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,10,12]]},"reference":[{"key":"2026041405270789700_ddx381-B1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nature02621","article-title":"Pathways towards and away from Alzheimer\u2019s disease","volume":"430","author":"Mattson","year":"2004","journal-title":"Nature"},{"key":"2026041405270789700_ddx381-B2","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nchem.247","article-title":"Amyloid-beta protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease","volume":"1","author":"Bernstein","year":"2009","journal-title":"Nat. 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