Villalba M, Pereira R, Martinez-Serrano A, Satrústegui J
Departamento de Biología-Molecular, Centro de Biología Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Spain.
Neurobiol Aging. 1995 Sep-Oct;16(5):809-16. doi: 10.1016/0197-4580(95)00087-u.
A deficient regulation of neuronal cytosolic calcium levels has been suggested to play a role in the pathogenesis of neurodegeneration. However, evidence for an alteration in cytosolic calcium regulation in old age is at present controversial. The present work was aimed at studying whether changes in synaptosomal calcium homeostasis in 30-month-old rats are uniform throughout the brain or affect specific brain regions. A second question addressed in this work is whether the effect of ageing on calcium homeostasis is restricted to the nerve terminal or a more general process affecting also cell bodies. To study these questions cytosolic calcium regulation was studied in parallel in synaptosomes and a preparation of acutely dissociated brain cells obtained from different regions of 3- and 30-month-old rats. 45Ca2+ accumulation and distribution in mitochondria (assessed as FCCP-releasable 45Ca2+) was also studied. Mean [Ca2+]i obtained at rest and after high K+ depolarization were unchanged in cerebral cortex synaptosomes but increased in hippocampal synaptosomes at 30 months. Resting [Ca2+]i also increased with age in hippocampal, but not cerebral cortex cells, whereas the increase in [Ca2+]i obtained by depolarization was larger in both brain regions. Calcium compartmentation in mitochondria from hippocampal neurons incubated under high K+ conditions was also decreased with ageing. An altered calcium regulation in cell bodies and synaptic terminals in the hippocampus may be involved in the development of functional impairments in the hippocampal formation.
神经元胞质钙水平调节缺陷被认为在神经退行性病变的发病机制中起作用。然而，目前关于老年时胞质钙调节改变的证据存在争议。本研究旨在探讨30月龄大鼠突触体钙稳态的变化在全脑是否一致，还是影响特定脑区。本研究涉及的另一个问题是，衰老对钙稳态的影响是否仅限于神经末梢，还是一个也影响细胞体的更普遍过程。为研究这些问题，我们同时研究了3月龄和30月龄大鼠不同脑区来源的突触体和急性解离脑细胞制剂中的胞质钙调节。还研究了45Ca2+在线粒体中的积累和分布（通过FCCP可释放的45Ca2+评估）。30月龄时，大脑皮质突触体静息和高钾去极化后的平均[Ca2+]i未改变，但海马突触体中的平均[Ca2+]i增加。海马细胞静息[Ca2+]i也随年龄增加，但大脑皮质细胞未增加，而两个脑区去极化后[Ca2+]i的增加更大。高钾条件下孵育的海马神经元线粒体中的钙分隔也随衰老而减少。海马中细胞体和突触末梢钙调节的改变可能与海马结构功能障碍的发生有关。
