Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice.

TitleInsulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice.
Publication TypeJournal Article
Year of Publication2015
AuthorsYu Y, Li X, Blanchard J, Li Y, Iqbal K, Liu F, Gong C-X
JournalJ Neural Transm (Vienna)
Volume122
Issue4
Pagination593-606
Date Published2015 Apr
ISSN1435-1463
KeywordsAlzheimer Disease, Animals, Body Weight, Brain, Disease Models, Animal, Exploratory Behavior, Female, Hypoglycemic Agents, Learning Disabilities, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Neuroimmunomodulation, Neuroprotective Agents, Nootropic Agents, Phosphorylation, Pioglitazone, Proto-Oncogene Proteins c-akt, Rosiglitazone, Spatial Learning, tau Proteins, Thiazolidinediones
Abstract

Sporadic Alzheimer's disease (AD) is a multifactorial metabolic brain disorder characterized by progressive neurodegeneration. Decreased brain energy and glucose metabolism occurs before the appearance of AD symptoms and worsens while the disease progresses. Deregulated brain insulin signaling has also been found in AD recently. To restore brain insulin sensitivity and glucose metabolism, pioglitazone and rosiglitazone, two insulin sensitizers commonly used for treating type 2 diabetes, have been studied and shown to have some beneficial effects in AD mouse models. However, the molecular mechanisms of the beneficial effects remain elusive. In the present study, we treated the 3xTg-AD mice, a widely used mouse model of AD, with pioglitazone and rosiglitazone for 4 months and studied the effects of the treatments on cognitive performance and AD-related brain alterations. We found that the chronic treatment improved spatial learning, enhanced AKT signaling, and attenuated tau hyperphosphorylation and neuroinflammation. These findings shed new light on the possible mechanisms by which these two insulin sensitizers might be useful for treating AD and support further clinical trials evaluating the efficacy of these drugs.

DOI10.1007/s00702-014-1294-z
Alternate JournalJ Neural Transm (Vienna)
PubMed ID25113171
Related Institute: 
Brain Health Imaging Institute (BHII)

Weill Cornell Medicine
Department of Radiology
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