Dietary niacin and brain function

临床烟酸缺乏症在发展中国家仍然是一个问题，而亚临床缺乏症在富裕国家仍然存在。烟酸缺乏症与酒精滥用有关，可导致严重的认知问题，从而增强疾病的影响。烟酸毒性的风险也是当前的一个问题，因为许多成年人消耗克量的烟酸来降低血液胆固醇，而一些有患上IDDM风险的儿童正在消耗类似量的烟酰胺。糙皮病是由严重的烟酸缺乏引起的人类疾病，其部分特征是显著的痴呆。这种痴呆症的范围可能从抑郁症到幻觉，再到类似精神分裂症的行为。神经系统症状在烟酸补充后数小时内显著缓解，表明烟酸参与神经传递的生物化学。烟酸是合成烟酸腺嘌呤二核苷酸磷酸（NAADP）和环状ADP-核糖所必需的，已知钙信号分子可调节大脑神经元之间的突触效率。我们的假设是，烟酸缺乏和药物补充会影响神经元功能，导致学习和记忆，社会交往和其他行为的变化。我们已经证明，缺乏一种制造环ADP核糖的酶的小鼠会表现出过度活跃的行为。 我们还表明，烟酸缺乏和大剂量的原因减少和增加环ADP-核糖水平，分别在大鼠大脑中，和大鼠解决空间学习任务的能力响应烟酸的状态。 我们目前正在开发一种更成熟的大鼠烟酸缺乏症模型，以观察更大范围的行为，并检查色氨酸代谢物在这些干扰中的作用。由于缺乏烟酸状态和脑功能领域的知识，这些基础实验对于开发有效的动物模型至关重要，这将使我们能够确定不同形式烟酸的安全摄入量范围，并探索烟酸在脑功能中的作用。从长远来看，现在了解烟酸缺乏导致痴呆症可能会为治疗精神分裂症等疾病提供线索。

Clinical niacin deficiency remains a problem in developing countries while subclinical deficiency persists in affluent countries. Niacin deficiency is observed with alcohol abuse and can lead to serious cognitive problems that enhance the impact of the disease. The risk of niacin toxicity is also a current issue as many adults consume gram quantities of nicotinic acid to lower blood cholesterol and some children at risk of developing IDDM are consuming similar quantities of nicotinamide. Pellagra, the disease in humans caused by severe niacin deficiency, is characterized, in part, by a striking dementia. This dementia may range from depression through hallucinations to behavior similar to schizophrenia. The neurological symptoms are dramatically relieved within hours after niacin supplementation, showing that niacin is involved in the biochemistry of nervous transmission. Niacin is required for the synthesis of nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose, calcium signaling molecules known to regulate synaptic efficiency between neurons in the brain. Our hypothesis is that niacin deficiency and pharmacological supplementation will affect neuron function, leading to changes in learning and memory, social interactions and other behaviors. We have shown that mice lacking one of the enzymes that makes cyclic ADP-ribose display hyperactive behavior.  We have also shown that niacin deficiency and megadosing cause decreased and increased cyclic ADP-ribose levels, respectively, in rat brain, and that the ability of rats to solve spatial learning tasks responds to niacin status.  We are currently developing a model of niacin deficiency in more mature rats to look at a greater range of behaviors, and to examine the role of tryptophan metabolites in these disturbances. Given the lack of knowledge in the area of niacin status and brain function, these basic experiments are essential to develop effective animal models which will allow us to determine safe intakes ranges for different forms of niacin, and to explore the roles that niacin plays in brain function. In the long term, learning now niacin deficiency causes dementia may provide clues in the treatment of conditions like schizophrenia.