Wu A, Molteni R, Ying Z, Gomez-Pinilla F
Department of Physiological Science, University of California at Los Angeles, 621 Charles E Young Drive, Los Angeles, CA H-1450, USA.
Neuroscience. 2003;119(2):365-75. doi: 10.1016/s0306-4522(03)00154-4.
We have conducted studies to determine the potential of dietary factors to affect the capacity of the brain to compensate for insult. Rats were fed with a high-fat sucrose (HFS) diet, a popularly consumed diet in industrialized western societies, for 4 weeks before a mild fluid percussion injury (FPI) or sham surgery was performed. FPI impaired spatial learning capacity in the Morris water maze, and these effects were aggravated by previous exposure of the rats to the action of the HFS diet. Learning performance decreased according to levels of brain-derived neurotrophic factor (BDNF) in individual rats, such that rats with the worst learning efficacy showed the lowest levels of BDNF in the hippocampus. BDNF immunohistochemistry localized the decreases in BDNF to the CA3 and dentate gyrus of the hippocampal formation. BDNF has a strong effect on synaptic plasticity via the action of synapsin I and cAMP-response element-binding protein (CREB), therefore, we assessed changes in synapsin I and CREB in conjunction with BDNF. Levels of synapsin I and CREB decreased in relation to decreases in BDNF levels. The combination of FPI and the HFS diet had more dramatic effects on the active state (phosphorylated) of synapsin I and CREB. There were no signs of neurodegeneration in the hippocampus of any rat group assessed with Fluoro-Jade B staining. The results suggest that FPI and diet impose a risk factor to the molecular machinery in charge of maintaining neuronal function under homeostatic and challenging situations.
我们开展了多项研究，以确定饮食因素影响大脑对损伤进行代偿能力的可能性。在进行轻度液压冲击伤（FPI）或假手术前4周，用高脂肪蔗糖（HFS）饮食喂养大鼠，HFS饮食是西方工业化社会中普遍食用的一种饮食。FPI损害了大鼠在莫里斯水迷宫中的空间学习能力，而此前大鼠接触HFS饮食的行为会加剧这些影响。个体大鼠的学习表现根据脑源性神经营养因子（BDNF）水平而下降，即学习效果最差的大鼠海马体中BDNF水平最低。BDNF免疫组化显示海马结构的CA3区和齿状回中BDNF水平降低。BDNF通过突触结合蛋白I和环磷酸腺苷反应元件结合蛋白（CREB）的作用对突触可塑性有强烈影响，因此，我们结合BDNF评估了突触结合蛋白I和CREB的变化。突触结合蛋白I和CREB的水平随着BDNF水平的降低而降低。FPI和HFS饮食的联合作用对突触结合蛋白I和CREB的活性状态（磷酸化状态）有更显著的影响。用Fluoro-Jade B染色评估的任何大鼠组的海马体中均未出现神经退行性变的迹象。结果表明，FPI和饮食对在稳态和应激情况下负责维持神经元功能的分子机制构成了危险因素。
