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Early intervention with glucagon-like peptide 1 analog liraglutide prevents tau hyperphosphorylation in diabetic db/db mice.
- Source :
-
Journal of neurochemistry [J Neurochem] 2015 Oct; Vol. 135 (2), pp. 301-8. Date of Electronic Publication: 2015 Aug 11. - Publication Year :
- 2015
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Abstract
- Increasing evidence has shown that type 2 diabetes (T2D) is a risk factor for Alzheimer's disease. Neurofibrillary tangles, which consist of hyperphosphorylated tau and misfolded microtubules, is one of the neuropathological hallmarks of Alzheimer's disease. Db/db mice, a rodent model of T2D, also exhibited age-dependent tau hyperphosphorylation. Glucagon-like peptide-1 (GLP-1) mimetics, a type of drug used in T2D, has been found to have neuroprotective effects. The aim of this study was to explore the potential effects of liraglutide (a GLP-1 analog), or insulin, on tau phosphorylation in T2D animals. Male db/db mice (3-3.5 weeks) were daily injected subcutaneously with liraglutide (n = 27), insulin (n = 27), or saline (n = 26), and five to seven mice were killed every 2 weeks for analysis of plasma and cerebrospinal (CSF) insulin levels by ELISA, and protein levels in the hippocampal formation by western blot. We found that db/db mice treated with saline exhibited an age-dependent decrease in CSF insulin and an increase in hippocampal tau phosphorylation. Liraglutide injection reversed the CSF insulin to ~1 mIU/L by the end of 8 weeks treatment, and prevented the hyperphosphorylation of tau protein in the hippocampal formation. By contrast, insulin injection had no effects on CSF insulin or phosphorylation of tau protein. In summary, this study indicates that early GLP-1 analog intervention prevented the age-dependent tau hyperphosphorylation in T2D mice brain, probably by facilitating sequential activation in an insulin signaling pathway reflected in increased basal activation of Akt and basal suppression of glycogen synthase kinase-3 beta.<br /> (© 2015 International Society for Neurochemistry.)
- Subjects :
- Animals
Blood Glucose analysis
Blood Glucose metabolism
Brain Chemistry drug effects
Diabetes Mellitus, Experimental complications
Glycogen Synthase Kinase 3 metabolism
Hippocampus drug effects
Hippocampus metabolism
Insulin blood
Insulin cerebrospinal fluid
Insulin pharmacology
Insulin Resistance
Male
Mice
Oncogene Protein v-akt biosynthesis
Weight Gain drug effects
Diabetes Mellitus, Experimental metabolism
Diabetic Neuropathies prevention & control
Hypoglycemic Agents therapeutic use
Liraglutide therapeutic use
Phosphorylation drug effects
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 135
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26183127
- Full Text :
- https://doi.org/10.1111/jnc.13248