Role of GluN2A and GluN2B subunits in the formation of filopodia and secondary dendrites in cultured hippocampal neurons.
GluN receptors are heteromers of obligatory GluN1 subunits and GluN2(A-D) subunits. In the present study, we addressed the question whether GluN2A and GluN2B subunits play distinct roles in the formation of filopodia and dendrites during the early development of hippocampal neurons. In hippocampal neurons brought into culture at embryonic day 17, we studied 2-3 days later the effects of N-methyl-D-aspartic acid (NMDA) on the numbers of filopodia, growth cones, and primary as well as secondary dendrites. Antagonists specific for GluN2A and GluN2B subunits were applied together with NMDA. NMDA only induced the formation of filopodia and secondary dendrites. Whereas filopodia were generated within 15 min by NMDA alone, secondary dendrites were only induced by the joint application of NMDA and the Rho kinase inhibitor Y-27632 for 24 h. The GluN2B antagonists ifenprodil and Ro 25-6981 prevented the NMDA-induced formation of filopodia, whereas the GluN2A antagonists NVP-AAM007 and EAA-090 prevented the formation of secondary dendrites. We conclude that both GluN2 subunits have differential roles in dendritic arborization.
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität, Albertstr. 25, 79104 Freiburg, Germany.
Frank
F
Henle
Martina
M
Dehmel
Jost
J
Leemhuis
Catharina
C
Fischer
Dieter K
DK
Meyer
D000818:Animals; D053961:Azabicyclo Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D063065:Organophosphonates / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000502:physiology; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D053961:Azabicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D063065:Organophosphonates; D010636:Phenols; D010880:Piperidines; D021122:Protein Subunits; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C498554:5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione; C121001:NR2B NMDA receptor; C109643:Ro 25-6981; C110623:EAA-090; C010739:ifenprodil