Gruol D L, Parsons K L
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Brain Res. 1996 Jul 29;728(2):166-74. doi: 10.1016/0006-8993(96)00185-0.
The effect of chronic alcohol (33 mM ethanol) on Ca2+ signals elicited by glutamate receptor agonists (quisqualate and NMDA) was examined in developing cerebellar Purkinje and granule neurons in culture. The neurons were exposed to alcohol during the second week in culture, the main period of morphological and physiological development. The Ca2+ signals were measured with fura-2 based microscopic video imaging. Chronic exposure to alcohol during development significantly reduced the peak amplitude of the Ca2+ signals to quisqualate (1 microM; Quis) in both the somatic and dendritic regions of the Purkinje neurons. The dendritic region was affected to a greater extent than the somatic region. Granule neurons also showed a reduced somatic Ca2+ signal to Quis (dendrites not measured) in the alcohol-treated cultures, indicating that the effect was not limited to Purkinje neurons. In addition to the effects on in the response to Quis, the peak amplitude of the Ca2+ signals to NMDA (100 microM) was reduced by chronic alcohol exposure during development in both the cultured Purkinje and granule neurons. Resting Ca2+ levels were not consistently affected by alcohol treatment in either neuronal type. These results indicate that Ca2+ signaling linked to glutamate receptor activation is an important target of alcohol in the developing nervous system and could be a contributing factor in the altered CNS function and development observed in animal models of fetal alcohol syndrome.
在培养的发育中小脑浦肯野神经元和颗粒神经元中，研究了慢性酒精（33 mM乙醇）对谷氨酸受体激动剂（quisqualate和NMDA）引发的Ca2+信号的影响。在培养的第二周，即形态和生理发育的主要时期，将神经元暴露于酒精中。使用基于fura-2的显微视频成像测量Ca2+信号。发育过程中慢性暴露于酒精显著降低了浦肯野神经元胞体和树突区域对quisqualate（1 microM；Quis）的Ca2+信号峰值幅度。树突区域比胞体区域受到的影响更大。在酒精处理的培养物中，颗粒神经元对Quis的胞体Ca2+信号也降低（未测量树突），表明这种影响不限于浦肯野神经元。除了对Quis反应的影响外，发育过程中慢性酒精暴露还降低了培养的浦肯野神经元和颗粒神经元对NMDA（100 microM）的Ca2+信号峰值幅度。两种神经元类型的静息Ca2+水平均未因酒精处理而受到一致影响。这些结果表明，与谷氨酸受体激活相关的Ca2+信号传导是发育中神经系统中酒精的一个重要靶点，并且可能是胎儿酒精综合征动物模型中观察到的中枢神经系统功能和发育改变的一个促成因素。
