Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

TitleAge-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2013
AuthorsSancheti H, Akopian G, Yin F, Brinton RD, Walsh JP, Cadenas E
JournalPLoS One
Volume8
Issue7
Paginatione69830
Date Published2013
ISSN1932-6203
KeywordsAge Factors, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Glucose, Insulin, Mice, Mice, Inbred C57BL, Molecular Mimicry, Neuronal Plasticity, Synapses, Thioctic Acid
Abstract

Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits) and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD) that shows progression of pathology as a function of age; two age groups: 6 months (young) and 12 months (old) were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O) and long term potentiation (LTP) (measured by electrophysiology). Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

DOI10.1371/journal.pone.0069830
Alternate JournalPLoS ONE
PubMed ID23875003
PubMed Central IDPMC3714252
Grant ListR01 AG016718 / AG / NIA NIH HHS / United States
P01AG026572 / AG / NIA NIH HHS / United States
R01AG016718 / AG / NIA NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D
Fei Yin, Ph.D.