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Val 8 ‐GLP‐1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats
Author(s) -
Wang XiaoHui,
Yang Wei,
Hölscher Christian,
Wang ZhaoJun,
Cai HongYan,
Li QingShan,
Qi JinShun
Publication year - 2013
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23181
Subject(s) - excitatory postsynaptic potential , neuroprotection , inhibitory postsynaptic potential , postsynaptic potential , postsynaptic current , neurotransmission , calcium in biology , medicine , postsynaptic density , chemistry , endocrinology , calcium , intracellular , neuroscience , biophysics , biology , biochemistry , receptor
Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD) in the elderly. Glucagon‐like peptide‐1 (GLP‐1), a modulator in T2DM therapy, has been shown to have neuroprotective properties. However, the native GLP‐1 can be rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV); the neuroprotective mechanism of GLP‐1 in the central nervous system is still an open question, and whether GLP‐1 can prevent amyloid β (Aβ)‐induced synaptic dysfunction and calcium disorder is still unclear. The present study, by using patch clamp and calcium imaging techniques, investigated the effects of Val 8 ‐GLP‐1(7–36), a GLP‐1 analogue with profound resistance to DPP IV, on the excitatory and inhibitory synaptic transmission and intracellular calcium concentration ([Ca 2+ ] i ) in the absence or presence of Aβ1–40. The results showed that 1) Aβ1–40 significantly reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in CA1 pyramidal neurons of rat brain slices; 2) Val 8 ‐GLP‐1(7–36) did not affect the activity of miniature postsynaptic currents but effectively protected against the Aβ1–40‐induced decrease in mEPSC and mIPSC frequency; 3) Aβ1–40 significantly increased [Ca 2+ ] i in primary neuronal cultures; and 4) Val 8 ‐GLP‐1(7–36) alone did not change the intracellular calcium level but prevented Aβ1–40‐induced persistent elevation of [Ca 2+ ] i . These findings demonstrate for the first time that central application of Val 8 ‐GLP‐1(7–36) could protect against Aβ‐induced synaptic dysfunction and intracellular calcium overloading, suggesting that the neuroprotection of GLP‐1 may be involved in the remodeling of synaptic activity and intracellular calcium homeostasis in the brain. © 2013 Wiley Periodicals, Inc.