Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology.
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 beta-catenin was increased probably as a result of its stabilization by glycogen synthase kinase-3beta 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…
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GSK-3β inhibition reduces tau hyperphosphorylation and neurofibrillary tangle formation in tau-overexpressing transgenic mice.
“Inhibition of GSK-3β may have dual benefits given that GSK-3β inhibition reduces tau hyperphosphorylation and NFT formation in tau-overexpressing transgenic mice (Noble et al., 2005; Engel et al., 2006; Leroy et al., 2010) and produces anticonvulsant effects against pentylenetetrazol-induced seizures in zebrafish larvae (Aourz et al., 2019).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Leroy et al., 2010
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- Authors
- Leroy, K., Ando, K., Héraud, C., Yilmaz, Z., Authelet, M., Boeynaems, J.-M., Buée, L., De Decker, R., & Brion, J.-P.
- Affiliations
- Université Libre de Bruxelles (BE)
- Laboratory of Histology, Neuroanatomy and Neuropathology, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium
- Inserm (FR)
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-01-07
- Volume
- 19
- Issue
- 2
- Pages
- 705-719
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1700634873
- Cited by
- 103
- References
- 60
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 9 · 2012: 13
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- lithium, neurofibrillary tangles
- MeSH terms
- Age Factors, Analysis of Variance, Animals, Antibodies, Monoclonal, Brain, Disease Models, Animal, Dose-Response Relationship, Drug, Exploratory Behavior, Humans, Mice, Transgenic, Microtubule-Associated Proteins, Motor Activity, Mutation, Nerve Tissue Proteins, Phosphorylation, Sciatic Nerve, Spinal Cord, Lithium Carbonate, Neurofibrillary Tangles, tau Proteins, Antimanic Agents, Tauopathies, Glycogen Synthase Kinase 3, Immunoprecipitation, Proto-Oncogene Proteins c-akt, Mice
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