Youssef Farid F, Ramchandani Jaya, Manswell Summer, McRae Amanda
Department of Preclinical Sciences, The University of the West Indies, St. Augustine Campus, Trinidad and Tobago.
Neurosci Lett. 2008 Jan 31;431(2):118-22. doi: 10.1016/j.neulet.2007.11.064. Epub 2007 Dec 14.
Lifelong calorie restriction is the only known intervention that has been shown to consistently increase life span and reduce the effects of aging on the brain. Given the difficulties of replicating lifelong calorie restriction within human populations, we have sought to assess the effects of short-term adult-onset calorie restriction upon acute excitotoxic insults in the rat hippocampus. Adult animals (approximately 6 months of age) underwent calorie restriction (alternate day feeding) for 7-10 weeks. Utilizing both electrophysiological and immunocytochemical techniques, we report that calorie restriction had no effect upon long-term potentiation (LTP), a measure of neuronal function. In control animals, application of kainic acid (20 microM) resulted in only 35% recovery of CA1 population spikes post-insult. However calorie-restricted animals showed significantly improved recovery after kainic acid treatment (64%). This data was supported by immunocytochemical studies which noted widespread loss of microtubule-associated protein (MAP 2) immunoreactivity in control slices following treatment with kainic acid; however MAP 2 staining was preserved in the CA1 and CA3 regions of calorie-restricted animals. Interestingly there was no significant difference in the recovery of population spikes between groups when slices were treated with N-methyl-d-aspartate (15 microM). We conclude that short-term adult-onset calorie restriction does not alter normal neuronal function and serves to protect the hippocampus from acute kainic acid excitotoxicity.
终生热量限制是唯一已知的、被证明能持续延长寿命并减轻衰老对大脑影响的干预措施。鉴于在人群中复制终生热量限制存在困难，我们试图评估成年后开始的短期热量限制对大鼠海马体急性兴奋性毒性损伤的影响。成年动物（约6个月大）接受了7至10周的热量限制（隔日喂食）。利用电生理和免疫细胞化学技术，我们报告热量限制对作为神经元功能指标的长时程增强（LTP）没有影响。在对照动物中，应用 kainic 酸（20微摩尔）导致损伤后CA1群体峰电位仅35%恢复。然而，热量限制的动物在 kainic 酸处理后显示出显著改善的恢复情况（64%）。免疫细胞化学研究支持了这一数据，该研究指出在用 kainic 酸处理后的对照切片中，微管相关蛋白（MAP 2）免疫反应性广泛丧失；然而，在热量限制动物的CA1和CA3区域，MAP 2染色得以保留。有趣的是，当切片用N-甲基-D-天冬氨酸（15微摩尔）处理时，各组之间群体峰电位的恢复没有显著差异。我们得出结论，成年后开始的短期热量限制不会改变正常的神经元功能，并有助于保护海马体免受急性 kainic 酸兴奋性毒性的影响。
