Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Leroy, Karellea; 1 | Ando, Kuniea; 1 | Héraud, Célinea | Yilmaz, Zehraa | Authelet, Michèlea | Boeynaems, Jean-Marieb | Buée, Lucc | De Decker, Roberta | Brion, Jean-Pierrea; *
Affiliations: [a] Laboratory of Histology, Neuroanatomy and Neuropathology, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium | [b] Laboratory of Medical Biology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium | [c] INSERM U837, Lille, France
Correspondence: [*] Corresponding author: Jean-Pierre Brion, Laboratory of Histology and Neuropathology, Université Libre de Bruxelles, School of Medicine, 808, route de Lennik, Bldg G, 1070 Brussels, Belgium. E-mail: [email protected].
Note: [1] These authors contributed equally to this study.
Abstract: Neurofibrillary tangles (NFTs) made of phosphorylated tau proteins are a key lesion of Alzheimer's disease and other neurodegenerative diseases, and previous studies have indicated that lithium can decrease tau phosphorylation in tau transgenic models. In this study, we have reassessed the effectiveness of treatment per os with lithium on the prevention, the arrest, or the reversal of NFT development in a tau transgenic line (Tg30tau) developing severe neurofibrillary pathology in the brain and the spinal cord. Wild-type and Tgtau30 mice were treated per os with lithium carbonate or with natrium carbonate by chronic chow feeding for 8 months starting at the age of 3 months (to test for a preventive effect on NFT formation) or by oral gavage for 1 month starting at the age of 9 months (after development of NFTs). In mice treated by oral gavage, a decrease of tau phosphorylation and of Sarkosyl-insoluble aggregated tau was observed in the brain and in the spinal cord. The density of NFTs identified by Gallyas staining in the hippocampus and in the spinal cord was also significantly reduced and was similar to that observed at the beginning of the lithium treatment. In these animals, the level of brain β-catenin was increased probably as a result of its stabilization by glycogen synthase kinase-3β inhibition. Despite this inhibitory effect of lithium on NFT development, the motor and working memory deficits were not significantly rescued in these aged animals. Chronic chow feeding with lithium did not alter the development of NFT. Nevertheless, this study indicates that even a relatively short-term per os treatment leading to high blood concentration of lithium is effective in arresting the formation of NFTs in the hippocampus and the spinal cord of a tau transgenic model.
Keywords: Lithium, neurofibrillary tangles, phosphorylation, tau, transgenic mouse, treatment
DOI: 10.3233/JAD-2010-1276
Journal: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 705-719, 2010
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
[email protected]
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office [email protected]
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
如果您在出版方面需要帮助或有任何建, 件至: [email protected]