Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype.

PloS One
Tiffany L SudduthDonna M Wilcock

Abstract

Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2-/- mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2-/- mice for a period of eight months, followed by water maze testing at 12 months of age, immediately prior to sacrifice. We found that lithium significantly lowered hyperphosphorylated tau levels as measured by Western blot and immunocytochemistry. However, we found no apparent neuroprotection, no effect on spatial memory deficits and an increase in histological amyloid deposition. Aβ levels measured biochemically were unaltered. We also found that lithium significantly altered the neuroinflammatory phenotype of the brain, resulting in enhanced alternative inflammatory response while concurrently lowering the classical inflammator...Continue Reading

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Citations

Aug 7, 2013·Pharmacology & Therapeutics·Margaret K KingEléonore Beurel
Jan 31, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tiffany L SudduthDonna M Wilcock
Nov 21, 2013·Acta Neuropathologica Communications·Laura Trujillo-EstradaJavier Vitorica
Oct 16, 2012·Neurobiology of Aging·Tiffany L SudduthDonna M Wilcock
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Jul 19, 2019·Frontiers in Molecular Neuroscience·Ashleigh DuthieCalum Sutherland
Jun 21, 2016·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Jeremy KoppelPeter Davies
Apr 29, 2021·Neural Regeneration Research·Matteo HauptThorsten R Doeppner

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Methods Mentioned

BETA
transgenic
ELISA
ubiquitination
PCR
protein assay

Software Mentioned

JMP
Nikon Elements BR
Odyssey Imaging
Graphpad Prism

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