Molteni R, Barnard R J, Ying Z, Roberts C K, Gómez-Pinilla F
Department of Physiological Science, University of California at Los Angeles, 621 Charles E. Young Drive, 90095, USA.
Neuroscience. 2002;112(4):803-14. doi: 10.1016/s0306-4522(02)00123-9.
We have investigated a potential mechanism by which a diet, similar in composition to the typical diet of most industrialized western societies rich in saturated fat and refined sugar (HFS), can influence brain structure and function via regulation of neurotrophins. We show that animals that learn a spatial memory task faster have more brain-derived neurotrophic factor (BDNF) mRNA and protein in the hippocampus. Two months on the HFS diet were sufficient to reduce hippocampal level of BDNF and spatial learning performance. Consequent to the action of BDNF on synaptic function, downstream effectors for the action of BDNF on synaptic plasticity were reduced proportionally to BDNF levels, in the hippocampus of rats maintained on the HFS diet between 2 and 24 months. In particular, animals maintained on the HFS diet showed a decrease in levels of: (i) synapsin I mRNA and protein (total and phosphorylated), important for neurotransmitter release; (ii) cyclic AMP-response element-binding protein (CREB) mRNA and protein (total and phosphorylated); CREB is required for various forms of memory and is under regulatory control of BDNF; (iii) growth-associated protein 43 mRNA, important for neurite outgrowth, neurotransmitter release, and learning and memory. Diet-related changes were specific for the hippocampus consequent to its role in memory formation, and did not involve neurotrophin-3, another member of the neurotrophin family. Our results indicate that a popularly consumed diet can influence crucial aspects of neuronal and behavioral plasticity associated with the function of BDNF.
我们研究了一种潜在机制，即一种成分与大多数工业化西方社会富含饱和脂肪和精制糖的典型饮食（HFS）相似的饮食，如何通过调节神经营养因子来影响大脑结构和功能。我们发现，空间记忆任务学习速度更快的动物海马体中脑源性神经营养因子（BDNF）的mRNA和蛋白质含量更高。食用HFS饮食两个月就足以降低海马体中BDNF的水平以及空间学习能力。由于BDNF对突触功能的作用，在2至24个月食用HFS饮食的大鼠海马体中，BDNF对突触可塑性作用的下游效应器与BDNF水平成比例降低。具体而言，食用HFS饮食的动物表现出以下物质水平降低：（i）突触素I的mRNA和蛋白质（总量及磷酸化形式），其对神经递质释放很重要；（ii）环磷酸腺苷反应元件结合蛋白（CREB）的mRNA和蛋白质（总量及磷酸化形式）；CREB是各种形式记忆所必需的，且受BDNF的调控；（iii）生长相关蛋白43的mRNA，其对神经突生长、神经递质释放以及学习和记忆很重要。与饮食相关的变化因海马体在记忆形成中的作用而对其具有特异性，且不涉及神经营养因子家族的另一个成员——神经营养因子-3。我们的研究结果表明，一种广泛食用的饮食可以影响与BDNF功能相关的神经元和行为可塑性的关键方面。
