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Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype.
PLoS One. 2012; 7(2):e31993.Plos

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 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.

Authors+Show Affiliations

Department of Physiology, University of Kentucky Sanders-Brown Center on Aging, Lexington, Kentucky, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22347510

Citation

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, pp. e31993.
Sudduth TL, Wilson JG, Everhart A, et al. Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype. PLoS ONE. 2012;7(2):e31993.
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 TL, et al. Lithium Treatment of APPSwDI/NOS2-/- Mice Leads to Reduced Hyperphosphorylated Tau, Increased Amyloid Deposition and Altered Inflammatory Phenotype. PLoS ONE. 2012;7(2):e31993. PubMed PMID: 22347510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lithium treatment of APPSwDI/NOS2-/- mice leads to reduced hyperphosphorylated tau, increased amyloid deposition and altered inflammatory phenotype. AU - Sudduth,Tiffany L, AU - Wilson,Joan G, AU - Everhart,Angela, AU - Colton,Carol A, AU - Wilcock,Donna M, Y1 - 2012/02/09/ PY - 2011/11/29/received PY - 2012/01/17/accepted PY - 2012/2/21/entrez PY - 2012/2/22/pubmed PY - 2012/8/1/medline SP - e31993 EP - e31993 JF - PloS one JO - PLoS ONE VL - 7 IS - 2 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22347510/Lithium_treatment_of_APPSwDI/NOS2_/__mice_leads_to_reduced_hyperphosphorylated_tau_increased_amyloid_deposition_and_altered_inflammatory_phenotype_ L2 - http://dx.plos.org/10.1371/journal.pone.0031993 DB - PRIME DP - Unbound Medicine ER -