Opposing regulation of tau protein levels by ionotropic and metabotropic glutamate receptors in human NT2 neurons

Human NT2-N neurons derived from retinoic acid treatment of the NTera 2 cell line were used to determine the consequences of ionotropic glutamate receptor (iGluR) hyperstimulation and possible modulatory role(s) exerted by metabotropic glutamate receptor (mGluR) activation. We found that NT2-N neurons express the NR1 subunit of N-methyl-D-aspartate (NMDA) iGluRs and mRNA encoding the la isoform of mGluRs. A 15 min pulse with 100 mu M NMDA induced an increase in the levels of tau proteins in NT2-N cells. This effect was prevented by incubating NT2-N neurons in the presence of the mGluR agonist(1S,3R)-1 aminocyclopentane-1,3-dicarboxylic acid (1S,SR-ACPD). This phenomenon was related, in terms of doses and time, with the observed 1S,3R-ACPD-mediated protection against NMDA-induced NT2-N cell death. Our findings suggest that iGluRs and mGluRs might participate in the control of human neuron viability by differentially affecting the expression of tau proteins. (C) 1998 Elsevier Science Ireland Ltd.