Sam and Rose Stein Institute for Research on Aging, Department of Psychiatry, School of Medicine, University of California, San Diego, CA 92093-0603, USA.
Neurosci Lett. 2012 May 10;516(1):161-5. doi: 10.1016/j.neulet.2012.03.092. Epub 2012 Apr 6.
Aging-related dysregulation of neuronal calcium metabolism, which not only involves the control of calcium fluxes but also the cytosolic calcium buffering system such as calbindin-1 (Calb1), may disturb synaptic plasticity and thereby memory functioning. Calb1 expression has been shown to affect hippocampal long-term potentiation and learning and to play a neuroprotective role in animal models of ischemic brain injury and neurodegenerative disorders. We hypothesize that memory performance in aged mice correlates with neuronal Calb1 protein expression in the hippocampal formation. We studied a set of 18 aged and 22 young male C57BL/6N mice, in which the aged group performed poorer than the young in single-trial novel object recognition testing (two-tailed p=0.005, U test). Apparent decreases in the Calb1 immunoreactivity (measured by quantitative immunohistochemistry) in aged mice compared to that in young mice were not statistically significant either in the hippocampal CA1 subfield or dentate gyrus. In the aged mouse group, levels of Calb1 immunoreactivity both in the CA1 subfield and dentate gyrus correlated directly with the measure of recognition memory performance (Spearman rank correlation r(s)=0.47 and 0.48, two-tailed p=0.047 and 0.044, respectively). Our results suggest that hippocampal Calb1 expression affects memory performance in aged mice probably via its role in maintaining neuronal calcium homeostasis. Alternatively, our finding of lower Calb1 immunoreactivity with poorer memory performance in aged mice might be attributed to saturation of Calb1 protein by higher levels of intracellular calcium, due to aging-related dysregulation of neuronal calcium fluxes.
与衰老相关的神经元钙代谢失调不仅涉及钙流的控制，还涉及细胞溶质钙缓冲系统，如钙结合蛋白 1（Calb1），可能会干扰突触可塑性，从而影响记忆功能。Calb1 的表达已被证明会影响海马长时程增强和学习，并在缺血性脑损伤和神经退行性疾病的动物模型中发挥神经保护作用。我们假设老年小鼠的记忆表现与海马结构中的神经元 Calb1 蛋白表达相关。我们研究了一组 18 只老年和 22 只年轻雄性 C57BL/6N 小鼠，其中老年组在单次新物体识别测试中的表现不如年轻组（双侧 p=0.005，U 检验）。与年轻小鼠相比，老年小鼠的 Calb1 免疫反应性（通过定量免疫组织化学测量）明显下降，但在海马 CA1 亚区或齿状回中并没有统计学意义。在老年小鼠组中，CA1 亚区和齿状回中的 Calb1 免疫反应性水平与识别记忆表现的测量值直接相关（Spearman 等级相关 r(s)=0.47 和 0.48，双侧 p=0.047 和 0.044）。我们的结果表明，海马 Calb1 表达可能通过维持神经元钙稳态来影响老年小鼠的记忆表现。或者，我们发现老年小鼠中 Calb1 免疫反应性较低与记忆表现较差可能归因于与衰老相关的神经元钙流失调导致细胞内钙水平升高而使 Calb1 蛋白饱和。
