Skip to main content

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

Publication ,  Journal Article
Sudduth, TL; Wilson, JG; Everhart, A; Colton, CA; Wilcock, DM
Published in: PLoS One
2012

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 inflammatory response. Our data suggest that lithium may be beneficial for the treatment of tauopathies but may not be beneficial for the treatment of Alzheimer's disease.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

2

Start / End Page

e31993

Location

United States

Related Subject Headings

  • tau Proteins
  • Treatment Outcome
  • Tauopathies
  • Phosphorylation
  • Nitric Oxide Synthase Type II
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Memory
  • Lithium
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sudduth, T. L., Wilson, J. G., Everhart, A., Colton, C. A., & Wilcock, D. M. (2012). Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype. PLoS One, 7(2), e31993. https://doi.org/10.1371/journal.pone.0031993
Sudduth, Tiffany L., Joan G. Wilson, Angela Everhart, Carol A. Colton, and Donna M. Wilcock. “Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype.PLoS One 7, no. 2 (2012): e31993. https://doi.org/10.1371/journal.pone.0031993.
Sudduth, Tiffany L., et al. “Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype.PLoS One, vol. 7, no. 2, 2012, p. e31993. Pubmed, doi:10.1371/journal.pone.0031993.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

2

Start / End Page

e31993

Location

United States

Related Subject Headings

  • tau Proteins
  • Treatment Outcome
  • Tauopathies
  • Phosphorylation
  • Nitric Oxide Synthase Type II
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Memory
  • Lithium