Peterson C, Neal J H, Cotman C W
Department of Psychobiology, University of California, Irvine 92717.
Brain Res Dev Brain Res. 1989 Aug 1;48(2):187-95. doi: 10.1016/0165-3806(89)90075-8.
Immature hippocampal neurons (E-18) were maintained in defined medium for up to 3 weeks and their susceptibility to N-methyl-D-aspartic acid (NMDA)-induced cell death was studied at various days in vitro. Upon acute exposure to NMDA (5 min), hippocampal neurons in vitro (8-12 days after plating) showed cell body swelling and dendritic degeneration that preceded cell death 24 h later. NMDA-induced neurodegeneration could be prevented by MK-801 treatment but not by tetrodotoxin. In contrast, immature (5-7 days old) neurons were unaltered by exposure to 500 microM NMDA for either 5 min or 24 h. One explanation for the resistance of immature neurons to glutamate neurotoxicity may be related to maturation of the NMDA receptor complex. Glutamate binding to the NMDA receptor in vivo increased from 14.6 +/- 1.6% (0 day) to 55.2 +/- 4.5% (day 7), 79 +/- 4.9% (day 14), 93.8 +/- 2.8% (day 21) until it reached the adult Sprague-Dawley value of 100 +/- 0.8% (day 90).
将未成熟的海马神经元（胚胎第18天）置于限定培养基中培养长达3周，并在体外培养的不同天数研究其对N-甲基-D-天冬氨酸（NMDA）诱导的细胞死亡的易感性。急性暴露于NMDA（5分钟）后，体外培养的海马神经元（接种后8 - 12天）出现细胞体肿胀和树突退化，24小时后细胞死亡。MK-801处理可预防NMDA诱导的神经变性，但河豚毒素不能。相比之下，未成熟（5 - 7天大）的神经元暴露于500微摩尔NMDA 5分钟或24小时后无变化。未成熟神经元对谷氨酸神经毒性具有抗性的一种解释可能与NMDA受体复合物的成熟有关。体内谷氨酸与NMDA受体的结合从14.6±1.6%（第0天）增加到55.2±4.5%（第7天）、79±4.9%（第14天）、93.8±2.8%（第21天），直至达到成年Sprague-Dawley大鼠的100±0.8%（第90天）的值。
