(Val⁸) glucagon-like peptide-1 prevents tau hyperphosphorylation, impairment of spatial learning and ultra-structural cellular damage induced by streptozotocin in rat brains.

It has being shown that glucagon-like peptide-1 (GLP-1), a new anti-diabetes agent, significantly attenuated beta-amyloid (Aβ) levels in rats. In the present study, (Val(8))GLP-1 was used to prevent impairments in memory formation, tau hyperphosphorylation and ultra-structural changes induced by streptozotocin intracerebroventricular (i.c.v.) injection. A spatial water maze task was used to test the rats' learning and memory formation, Western blot was used to measure tau hyperphosphorylation/total tau, and transmission electron microscope was used to find ultra-structural changes. The results shown that streptozotocin induced a series of Alzheimer disease -like changes in behaviour, a significant decline in learning and memory formation, an increased expression of total tau and an increased ratio of phosphorylated tau, and damage to nucleus and nucleolus as seen in electron micrographs. After treatment with (Val(8))GLP-1 (50 μM in 10 μl i.c.v.), there is a significant improvement in learning and memory, a reduction in total tau expression and hyperphosphorylated tau levels, and a recovery of damaged cell nuclei and nucleolus. Our results indicated that (Val(8))GLP-1 might prevent age-related neurodegenerative changes by preventing decline of learning and memory formation, reduction of phosphorylated tau levels and protection of subcellular structures and morphology of neurons. Therefore, (Val(8))GLP-1 is potentially a novel treatment for Alzheimer's disease.