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 1a isoform of mGluRs. A 15 min pulse with 100 microM 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 (1 S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-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.
Paterlini
M
M
Department of Biomedical Sciences and Biotechnologies, Brescia University Medical School, Italy. paterlin@med.unibs.it
Valerio
A
A
Baruzzi
F
F
Memo
M
M
Spano
P F
PF
D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D009410:Nerve Degeneration / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000235:genetics*; D016875:tau Proteins / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016875:tau Proteins; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016202:N-Methylaspartate