TY - JOUR T1 - Glucagon-Like Peptide-1 Cleavage Product GLP-1(9-36) Amide Rescues Synaptic Plasticity and Memory Deficits in Alzheimer's Disease Model Mice JF - The Journal of Neuroscience JO - J. Neurosci. SP - 13701 LP - 13708 DO - 10.1523/JNEUROSCI.2107-12.2012 VL - 32 IS - 40 AU - Tao Ma AU - Xueliang Du AU - Joseph E. Pick AU - Guangzhi Sui AU - Michael Brownlee AU - Eric Klann Y1 - 2012/10/03 UR - http://www.jneurosci.org/content/32/40/13701.abstract N2 - Glucagon-like peptide-1 (GLP-1) is an endogenous intestinal peptide that enhances glucose-stimulated insulin secretion. Its natural cleavage product GLP-1(9-36)amide possesses distinct properties and does not affect insulin secretion. Here we report that pretreatment of hippocampal slices with GLP-1(9-36)amide prevented impaired long-term potentiation (LTP) and enhanced long-term depression induced by exogenous amyloid β peptide Aβ(1–42). Similarly, hippocampal LTP impairments in amyloid precursor protein/presenilin 1 (APP/PS1) mutant mice that model Alzheimer's disease (AD) were prevented by GLP-1(9-36)amide. In addition, treatment of APP/PS1 mice with GLP-1(9-36)amide at an age at which they display impaired spatial and contextual fear memory resulted in a reversal of their memory defects. At the molecular level, GLP-1(9-36)amide reduced elevated levels of mitochondrial-derived reactive oxygen species and restored dysregulated Akt–glycogen synthase kinase-3β signaling in the hippocampus of APP/PS1 mice. Our findings suggest that GLP-1(9-36)amide treatment may have therapeutic potential for AD and other diseases associated with cognitive dysfunction. ER -