Dietary niacin and brain function

临床烟酸缺乏在发展中国家仍然是一个问题，而亚临床烟酸缺乏在富裕国家仍然存在。烟酸缺乏与酗酒有关，并可能导致严重的认知问题，从而增强疾病的影响。烟酸中毒的风险也是当前的一个问题，因为许多成年人摄入克量的烟酸来降低血液胆固醇，一些有患IDDM风险的儿童正在摄入类似数量的烟酰胺。青光眼是一种由严重的烟酸缺乏引起的人类疾病，其部分特征是明显的痴呆症。这种痴呆症的范围从抑郁到幻觉，再到类似精神分裂症的行为。补充烟酸后数小时内神经症状显著缓解，表明烟酸参与了神经传递的生化过程。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，这两种钙信号分子可以调节大脑中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，导致学习记忆、社会互动和其他行为的改变。我们已经证明，缺乏一种使环状ADP-核糖产生的酶的小鼠表现出过度活跃的行为。我们还表明，烟酸缺乏和巨糖分别导致大鼠大脑中环状ADP-核糖水平降低和增加，并且大鼠解决空间学习任务的能力对烟酸状态做出反应。我们目前正在建立更成熟大鼠的烟酸缺乏模型，以观察更广泛的行为，并检查色氨酸代谢物在这些紊乱中的作用。鉴于对烟酸状态和脑功能领域知识的缺乏，这些基础实验对于开发有效的动物模型是必不可少的，这些动物模型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所起的作用。从长远来看，现在了解烟酸缺乏会导致痴呆症，可能会为精神分裂症等疾病的治疗提供线索。

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.