Bruce-Keller A J, Umberger G, McFall R, Mattson M P
Sanders-Brown Research Center on Aging, Department of Anatomy and Neurobiology, University of Kentucky, Lexington 40536-0230, USA.
Ann Neurol. 1999 Jan;45(1):8-15.
Food restriction (FR) in rodents is known to extend life span, reduce the incidence of age-related tumors, and suppress oxidative damage to proteins, lipids, and DNA in several organ systems. Excitotoxicity and mitochondrial impairment are believed to play major roles in the neuronal degeneration and death that occurs in the brains of patients suffering from both acute brain insults such as stroke and seizures, and chronic neurodegenerative conditions such as Alzheimer's, Parkinson's, and Huntington's diseases. We now report that FR (alternate-day feeding regimen for 2-4 months) in adult rats results in resistance of hippocampal neurons to excitotoxin-induced degeneration, and of striatal neurons to degeneration induced by the mitochondrial toxins 3-nitropropionic acid and malonate. FR greatly increased the resistance of rats to kainate-induced deficits in performance in water-maze learning and memory tasks, and to 3-nitropropionic acid-induced impairment of motor function. These findings suggest that FR not only extends life span, but increases resistance of the brain to insults that involve metabolic compromise and excitotoxicity.
众所周知，限制啮齿动物的食物摄入（FR）可延长其寿命，降低与年龄相关肿瘤的发病率，并抑制对几个器官系统中蛋白质、脂质和DNA的氧化损伤。兴奋性毒性和线粒体损伤被认为在患有急性脑损伤（如中风和癫痫发作）以及慢性神经退行性疾病（如阿尔茨海默病、帕金森病和亨廷顿病）患者大脑中发生的神经元变性和死亡中起主要作用。我们现在报告，成年大鼠的FR（2 - 4个月的隔日喂养方案）可使海马神经元对兴奋性毒素诱导的变性产生抗性，并使纹状体神经元对线粒体毒素3 -硝基丙酸和丙二酸诱导的变性产生抗性。FR大大增强了大鼠对在水迷宫学习和记忆任务中由红藻氨酸诱导的行为缺陷以及对3 -硝基丙酸诱导的运动功能损伤的抗性。这些发现表明，FR不仅能延长寿命，还能增强大脑对涉及代谢损害和兴奋性毒性损伤的抗性。
