衰老 CA1 海马锥体神经元中钙代谢的改变。
Altered calcium metabolism in aging CA1 hippocampal pyramidal neurons.
机构信息
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
出版信息
J Neurosci. 2013 May 1;33(18):7905-11. doi: 10.1523/JNEUROSCI.5457-12.2013.
Abstract
Altered neuronal calcium homeostasis is widely hypothesized to underlie cognitive deficits in normal aging subjects, but the mechanisms that underlie this change are unknown, possibly due to a paucity of direct measurements from aging neurons. Using CCD and two-photon calcium imaging techniques on CA1 pyramidal neurons from young and aged rats, we show that calcium influx across the plasma membrane increases with aging, and that this change is countered by increased intracellular calcium buffering. The additional buffer in aging neurons balances the increased calcium influx following a small number (<3) action potentials, but is overwhelmed during sustained or theta-like activity which leads to a greater rise in intracellular calcium concentration in aging than that in young neurons. Our results demonstrate that calcium overload occurs regularly in aging CA1 pyramidal neurons under physiological conditions. This overload may be a critical factor in age-related decline in hippocampus-dependent cognitive function.
摘要
神经元钙稳态的改变被广泛认为是正常衰老个体认知缺陷的基础，但导致这种变化的机制尚不清楚，这可能是由于缺乏来自衰老神经元的直接测量。通过使用 CCD 和双光子钙成像技术对年轻和年老大鼠 CA1 锥体神经元进行研究，我们发现质膜钙内流随着年龄的增长而增加，而这种变化被细胞内钙缓冲能力的增加所抵消。在年轻神经元中，这种额外的缓冲在少数（<3）动作电位后平衡了增加的钙内流，但在持续或类似 theta 的活动中被淹没，这导致衰老神经元中的细胞内钙浓度升高幅度大于年轻神经元。我们的结果表明，在生理条件下，衰老 CA1 锥体神经元中经常发生钙超载。这种过载可能是与年龄相关的海马依赖性认知功能下降的关键因素。
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