دورية أكاديمية
Hippocampal tau oligomerization early in tau pathology coincides with a transient alteration of mitochondrial homeostasis and DNA repair in a mouse model of tauopathy
| العنوان: | Hippocampal tau oligomerization early in tau pathology coincides with a transient alteration of mitochondrial homeostasis and DNA repair in a mouse model of tauopathy |
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| المؤلفون: | Zheng, Jin, Akbari, Mansour, Schirmer, Claire, Reynaert, Marie-Line, Loyens, Anne, Lefebvre, Bruno, Buée, Luc, Croteau, Deborah, Galas, Marie-Christine, Bohr, Vilhelm |
| المساهمون: | University of Copenhagen = Københavns Universitet (UCPH), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), National Institute on Aging Baltimore, MD, USA (NIH) |
| المصدر: | ISSN: 2051-5960 ; Acta Neuropathologica Communications ; https://inserm.hal.science/inserm-02999922Test ; Acta Neuropathologica Communications, 2020, 8 (1), pp.25. ⟨10.1186/s40478-020-00896-8⟩. |
| بيانات النشر: | HAL CCSD BioMed Central part of Springer Science |
| سنة النشر: | 2020 |
| المجموعة: | LillOA (HAL Lille Open Archive, Université de Lille) |
| مصطلحات موضوعية: | Mitochondrial homeostasis, Oxidative stress, Polymerase beta, Tau oligomerization, Tauopathies, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] |
| الوصف: | International audience ; Insoluble intracellular aggregation of tau proteins into filaments and neurodegeneration are histopathological hallmarks of Alzheimer disease (AD) and other tauopathies. Recently, prefibrillar, soluble, oligomeric tau intermediates have emerged as relevant pathological tau species; however, the molecular mechanisms of neuronal responses to tau oligomers are not fully understood. Here, we show that hippocampal neurons in six-month-old transgenic mouse model of tauopathy, THY-Tau22, are enriched with oligomeric tau, contain elongated mitochondria, and display cellular stress, but no overt cytotoxicity compared to the control mice. The levels of several key mitochondrial proteins were markedly different between the THY-Tau22 and control mice hippocampi including the mitochondrial SIRT3, PINK1, ANT1 and the fission protein DRP1. DNA base excision repair (BER) is the primary defense system against oxidative DNA damage and it was elevated in six-month-old transgenic mice. DNA polymerase β, the key BER DNA polymerase, was enriched in the cytoplasm of hippocampal neurons in six-month-old transgenic mice and localized with and within mitochondria. Polβ also co-localized with mitochondria in human AD brains in neurons containing oligomeric tau. Most of these altered mitochondrial and DNA repair events were specific to the transgenic mice at 6 months of age and were not different from control mice at 12 months of age when tau pathology reaches its maximum and oligomeric forms of tau are no longer detectable. In summary, our data suggests that we have identified key cellular stress responses at early stages of tau pathology to preserve neuronal integrity and to promote survival. To our knowledge, this work provides the first description of multiple stress responses involving mitochondrial homeostasis and BER early during the progression of tau pathology, and represents an important advance in the etiopathogenesis of tauopathies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32131898; inserm-02999922; https://inserm.hal.science/inserm-02999922Test; https://inserm.hal.science/inserm-02999922/documentTest; https://inserm.hal.science/inserm-02999922/file/s40478-020-00896-8.pdfTest; PUBMED: 32131898; PUBMEDCENTRAL: PMC7057491 |
| DOI: | 10.1186/s40478-020-00896-8 |
| الإتاحة: | https://doi.org/10.1186/s40478-020-00896-8Test https://inserm.hal.science/inserm-02999922Test https://inserm.hal.science/inserm-02999922/documentTest https://inserm.hal.science/inserm-02999922/file/s40478-020-00896-8.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.B5738C97 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s40478-020-00896-8 |
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