N-Methyl-D-aspartate receptors contribute to the maintenance of dopaminergic neurons in rat midbrain slice cultures.
Excitatory neuronal activity produces beneficial influences on neuronal survival under several circumstances. We show that cultivation of rat midbrain slices in the presence of elevated extracellular Mg(2+) resulted in a marked decrease in the number of dopaminergic neurons. The effect was prominent when Mg(2+) was added to the medium during the first week of cultivation. Chronic treatment with antagonists of N-methyl-D-aspartate receptors such as 2-amino-5-phosphonovaleric acid, MK-801 and ifenprodil also resulted in a marked loss of dopaminergic neurons, whereas nicotinic receptor antagonists showed no effect. The effect of MK-801 was abolished by chronic depolarization by elevated extracellular K(+), or by application of forskolin or dibutyryl cyclic AMP. Thus, tonic activation of N-methyl-D-aspartate receptors driven by neuronal activity may play an important role in the maintenance of dopaminergic neurons.
Katsuki
Hiroshi
H
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan.
Shibata
Haruki
H
Takenaka
Chikako
C
Kume
Toshiaki
T
Kaneko
Shuji
S
Akaike
Akinori
A
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008274:Magnesium / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D005576:Colforsin; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D012964:Sodium; D014446:Tyrosine 3-Monooxygenase; D008274:Magnesium; C010739:ifenprodil; D011188:Potassium; D004298:Dopamine