论文部分内容阅读
Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimers disease (AD) in the elderly.Glucagonlike peptide-1 (GLP-1), a modulator used in T2DM therapy, has been shown to have neuroprotective properties in AD.However, whether GLP-1 could prevent neurotoxic amyloid β (Aβ) peptide, a hallmark in the AD brain, is still unclear.The present study, by using hippocampal slice patch clamp and calcium image techniques, investigated the effects ofVal8-GLP-1(7-36), a GLP-1 analogue with greater biological activity, on the excitatory and inhibitory synaptic transmission and intracellular calcium concentration ([Ca2+]i) in the absence or in the presence of Aβ1-40.The results showed that: (1) Aβ1-40 (100 nM) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in CA1 pyramidal neurons of rat brain slices;(2)Val8GLP-1(7-36) (10 nM) did not affect the activity of miniature postsynaptic currents, but effectively protected against Aβ1-40-induced decrease in mEPSCs and mIPSCs frequency;(3) Aβ1-4o increased [Ca2+]i in primary neuronal cultures;(4) Val8-GLP-1(7-36) did not change the intracellular calcium level, but prevented Aβ1.40-induced elevation of [Ca2+]i.These findings demonstrate for the first time that Val8-GLP-1(7-36) could protect against Aβ-induced synaptic transmission disorder and intracellular calcium overloading, suggest that the functional upregulation of GLP-1 system in the brain might be a promising strategy for the treatment of AD, particularly when associate with T2DM.