AGING AND ALCOHOL ON NEURONAL CALCIUM METABOLISM

这个项目的总体目标是描述两国之间的关系 在衰老、急性和慢性乙醇注射和改变之间 神经细胞钙转运与钙依赖性刺激分泌 耦合。我们的普遍假设是，无论是乙醇注射还是 衰老导致通过钙通道进入的钙减少 神经元和神经元胞浆中钙代谢的变化。在……里面 联合、酒精和老化可能会促进减量的发生 在钙通道功能和加剧细胞内的变化 钙稳态。研究的目的是刻画 急、慢性酒精对电压依赖性钙离子动力学的影响 幼年小鼠突触体和突触神经体中的通道 年迈的雄性，费舍尔344只老鼠。实验将在七个大脑中进行 区域(大脑皮层、小脑、脑干、中脑、下丘脑、 海马体和纹状体)对衰老的敏感性不同 酒精。这些实验将同时检查(在相同的情况下 作为钙实验的样本)内源性多巴胺和去甲肾上腺素 释放以检测乙醇和衰老对刺激分泌的影响 耦合过程。将进行研究，以确定 年龄和急、慢性酒精对二氢吡啶敏感钙的影响 大脑区域突触体和突触神经体中的通道。大脑 要研究的地区将是如上所述的七个地区。这些 脑内不同区域二氢吡啶结合部位的分布不同。 最后，将进行研究，以确定急性和非传染性疾病的影响 慢性乙醇染毒对大鼠心肌细胞内游离钙离子浓度的影响 幼年大鼠与老年大鼠的突触体和突触神经体。这些研究 将在上述七个大脑区域上使用 细胞内钙指示剂Fura-2。

The overall aim of this project is to characterize the relationships between aging, acute and chronic ethanol administration and altered neuronal calcium transport and calcium-dependent stimulus-secretion coupling. Our general hypothesis is that both ethanol administration and aging result in a reduction in calcium entry through calcium channels into neurons and a change in calcium metabolism in the neuronal cytosol. In combination, ethanol and aging may facilitate the occurrence of decrements in calcium channel function and exacerbate the changes in intracellular calcium homeostasis. Studies are designed to characterize the influence of acute and chronic alcohol on the kinetics of voltage-dependent calcium channels in synaptosomes and synaptoneurosomes isolated from young versus old male, Fischer 344 rats. Experiments will be conducted in seven brain regions(cerebral cortex, cerebellum, brain stem, midbrain, hypothalamus, hippocampus and striatum) known to vary in sensitivity to aging and alcohol. these experiments will examine simultaneously (and in the sam samples as the calcium experiments) endogenous dopamine and norepinephrine release to examine the influence of ethanol and aging on stimulus-secretion coupling processes. Studies will be conducted to determine the effects of age and acute and chronic alcohol on dihydropyridine-sensitive calcium channels in brain regional synaptosomes and synaptoneurosomes. The brain regions to be studied will be the same seven as described above. These brain regions differ in the distribution of dihdropyridine binding sites. Finally, studies will be conducted to characterize the effects of acute and chronic ethanol administration on free, cytosolic calcium concentration of synaptosomes and synaptoneurosomes in young versus old rats. These studies will be conducted on the seven brain regions described above using the intracellular calcium indicator Fura-2.