AGING AND ALCOHOL ON NEURONAL CALCIUM METABOLISM

本项目的总体目标是描述 在衰老、急性和慢性乙醇给药之间， 神经元钙转运和钙依赖性刺激分泌 偶合器. 我们的一般假设是，乙醇管理和 衰老导致钙通过钙通道进入 神经元和神经元胞质中钙代谢的变化。 在 结合使用，乙醇和老化可能会促进减少的发生 在钙通道功能和加剧的变化， 钙稳态 研究旨在描述以下因素的影响 急性和慢性酒精对电压依赖性钙动力学的影响 突触体和突触神经体中的通道， 老年雄性，费舍尔344大鼠。 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， 海马和纹状体）已知对衰老的敏感性不同， 酒精 这些实验将同时进行（同时 样品作为钙实验）内源性多巴胺和去甲肾上腺素 释放，以检查乙醇和老化对刺激分泌的影响 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 脑区域突触体和突触神经体中的通道。 大脑 要研究的区域将是与上述相同的七个区域。 这些 脑区域在二氢吡啶结合位点的分布上不同。 最后，将进行研究，以确定急性和 慢性乙醇给药对细胞内游离钙离子浓度的影响 突触体和突触神经体。 这些研究 将在上述七个大脑区域进行， 细胞内钙离子指示剂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.