Effects Of Group Ⅰ MGluRs On Aβ_31-35-induced Neurotoxicity Of The Primary Cultured Cortical Neurons

Alzheimer Disease(AD)is a degenerative disease characterized by specific senile plaque (SP) and neurofibirilary tangle(NFT) andβ-amyliod(Aβ) deposition mainly found in cortical and hippocampal neurons. Previous study by our lab and other investigators have demonstrated that Aβ31-35 possesses the similar toxicity as full length of Aβpeptide which have proved the leading cause of AD.Glutamate(Glu) is the most important excited transmitter in the brain.Glu receptors are consist of two kinds of receptors: named inotropic glutamate receptors(iGluRs) and metabotropic glutamate receptors(mGluRs). Eight subtypes of mGluRs are classified into three distinct groups according to their sequence homology, pharmacological profile and signaling properties (I~III).Group I mGluRs(I mGluRs) include mGluR1 and mGluR5 which hydrolysis PI to IP3 and DG . Activation of I mGluRs increase [Ca2+]i by IP3-dependant release of Ca2+ from reticulum and also produces effects by DG-activated PKC. There are conflict reports concerning the effects of I mGluRs on neuronal insults, include that the I mGluRs mediate the neurotoxity and opposite report that they protect neurons against insults. Thus the present study was designed to explore the effects of I mGluRs including mGluR1 and mGluR5 on Aβ31-35- induced apoptosis and [Ca2+]i change of the primary cultured cortical neurons prepared from 1-day-old Sprague-Dawley rat cortex ; in which electrol microscope, flow cytometry of Annexin V-PI fluorescent staining and TdT mediated dUTP nick end labeling (TUNEL) were carried out . In addition, to anylasis the mechanisms underlying I mGluRs against Aβ31-35- induced apoptosis , the activities of Caspase-3, 8, 9 were measured to determine if the instrinsic and/or extrinsic dependent pathways were involved in apoptosis induced by Aβ31-35. Meanwhile examine the effects of PKC inhibitor BMI on DHPG-mediated neurotoxicity of Aβ31-35.Part I Effects of group I mGluRs on Aβ31-35-induced apoptosis of the primary cultured cortical neuronsIt has been demonstrated that Aβ1-42 and Aβ25-35 as well as Aβ31-35 are involved in neurotoxicity including induction of apoptosis and it has been also reported that I mGluRs possess neurotoxicity by elevation of [Ca2+]i , increase of neuronal excitability and potentiation...