Inhibiting neuronal migration by blocking NMDA receptors in the embryonic rat cerebral cortex: a tissue culture study.
To investigate the role of the NMDA receptor on neuronal migration in the cerebral cortex, we performed a tissue culture study using embryonic rat brain. After we labeled progenitor cells in the ventricular zone of E16 cerebral cortex explants by [3H]thymidine, the explants were cultured for 48 h. Then distribution of labeled cells was evaluated autoradiographically. Blocking NMDA receptors by adding the NMDA receptor antagonist, (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801: 1 or 10 microM) or d(-)-2-amino-5-phosphonopentanoic acid (d-AP5: 100 microM) to the culture medium, caused significantly decreased distribution of labeled cells in the outer intermediate zone (control 14.2+/-5.5%, 1 microM MK-801 5.8+/-7.2%, 10 microM MK-801 3.6+/-1.4%, and d-AP5 8.6+/-4.0%; mean+/-S.D.). This suggests that blocking NMDA receptors inhibits neuronal migration in the cerebral cortex. Furthermore, the influence of decreased intracellular Ca2+ concentration on neuronal migration was examined by adding intracellular Ca2+ chelator, 1, 2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester (BAPTA-AM: 5 or 25 microM). This also resulted in inhibited neuronal migration. Therefore, it seems that neuronal migration in the cerebral cortex is regulated by intracellular Ca2+ concentration, which the NMDA receptor may influence.
Hirai
K
K
Department of Pediatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. k.hirai@ped.kpu-m.ac.jp
Yoshioka
H
H
Kihara
M
M
Hasegawa
K
K
Sakamoto
T
T
Sawada
T
T
Fushiki
S
S
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium