Abstract

Type 2 diabetes has been identified as a risk factor for patients with Alzheimer's disease Insulin signalling is often impaired in Alzheimer's disease, contributing to the neurodegenerative process One potential strategy to help prevent this is the normalisation of insulin signalling in the brain Therefore, the present study was designed to test the effects of novel enzyme-resistant analogues of the insulin-releasing incretin hormone, glucagon-like peptide 1 (GLP-1) The effects of Liraglutide (Victoza) and other novel GLP-1 analogues were tested on synaptic plasticity (LTP) in area CA1 of the hippocampus At a dose of 15 nmol in 5 mu l i c v. Liraglutide (P < 0005), Asp(7)GLP-1 (P < 0001), N-glyc-GLP-1 (P < 001), and Pro(9)GLP-1 (P < 0.001). In contrast, the GLP-1 receptor antagonist exendin(9-39)amide impaired LTP (P < 0.001) Co-injection of exendin(9-39) and Liraglutide showed no effect oil LTP. These results clearly demonstrate that Liraglutide and other GLP-1 analogues elicit effects on neurotransmission in the brain Furthermore, GLP-1 peptides are not only effective in modulating insulin-release and achieving glycaemic control in type 2 diabetes, but are also effective in modulating synaptic plasticity These findings are consistent with our previous observations that the novel analogue (Val(8))GLP-1 enhances LTP and reverses the impairments of LTP induced by beta-amyoid fragments Therefore, the drug effects seen here could potentially ameliorate the impairments in neuronal communication and cognitive processes observed in Alzheimer's disease (C) 2009 Elsevier B V. All rights reserved