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Hyperphosphorylated Tau Relates to Improved Cognitive Performance and Reduced Hippocampal Excitability in the Young rTg4510 Mouse Model of Tauopathy.
Xolalpa-Cueva, Lorena; García-Carlos, Carlos Antonio; Villaseñor-Zepeda, Rocío; Orta-Salazar, Erika; Díaz-Cintra, Sofia; Peña-Ortega, Fernando; Perry, George; Mondragón-Rodríguez, Siddhartha.
Afiliación
  • Xolalpa-Cueva L; UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, Mexico.
  • García-Carlos CA; UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, Mexico.
  • Villaseñor-Zepeda R; UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, Mexico.
  • Orta-Salazar E; UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, Mexico.
  • Díaz-Cintra S; UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, Mexico.
  • Peña-Ortega F; UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, Mexico.
  • Perry G; UTSA Neuroscience Institute and Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
  • Mondragón-Rodríguez S; UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, Mexico.
J Alzheimers Dis ; 87(2): 529-543, 2022.
Article en En | MEDLINE | ID: mdl-35342085
BACKGROUND: Tau hyperphosphorylation at several sites, including those close to its microtubule domain (MD), is considered a key pathogenic event in the development of tauopathies. Nevertheless, we recently demonstrated that at the very early disease stage, tau phosphorylation (pTau) at MD sites promotes neuroprotection by preventing seizure-like activity. OBJECTIVE: To further support the notion that very early pTau is not detrimental, the present work evaluated the young rTg4510 mouse model of tauopathy as a case study. Thus, in mice at one month of age (PN30-35), we studied the increase of pTau within the hippocampal area as well as hippocampal and locomotor function. METHODS: We used immunohistochemistry, T-maze, nesting test, novel object recognition test, open field arena, and electrophysiology. RESULTS: Our results showed that the very young rTg4510 mouse model has no detectable changes in hippocampal dependent tasks, such as spontaneous alternation and nesting, or in locomotor activity. However, at this very early stage the hippocampal neurons from PN30-35 rTg4510 mice accumulate pTau protein and exhibit changes in hippocampal oscillatory activity. Moreover, we found a significant reduction in the somatic area of pTau positive pyramidal and granule neurons in the young rTg4510 mice. Despite this, improved memory and increased number of dendrites per cell in granule neurons was found. CONCLUSION: Altogether, this study provides new insights into the early pathogenesis of tauopathies and provides further evidence that pTau remodels hippocampal function and morphology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas tau / Tauopatías Límite: Animals / Humans Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: México Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas tau / Tauopatías Límite: Animals / Humans Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: México Pais de publicación: Países Bajos