Study on modulation of dopaminergic function via manipulation of tryptophan metabolism

通过操纵色氨酸代谢调节多巴胺能功能的研究

• 批准号: 20780100
• 负责人: FUKUWATARI Tsutomu
• 金额: $ 2.5万
• 依托单位: The University of Shiga Prefecture
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20780100/
• 关键词: 栄養化学; 神経伝達物質; アミノ酸; 脳機能; 神経疾患; 食事

Trypotphan metabolite kynurenic acid (KYNA) is a preferential antagonist of the α7 nicotinic acetylcholine receptor (α7nAChR). In vivo, nanomolar KYNA reduces the extracellular levels of dopamine in the brain via the blockade of α7nAChRs. However, little is known what physiological state affect KYNA production in the brain. In the present study, we examined the effects of several physiological factors such as hyperglycemia and hormone change on the KYNA production and dopaminergic function. Type I diabetes model rats, thyroxin administrated rats and ethanol administrated rats were examined, and the streptozotocin-induced type I diabetes model rats showed the increase of brain KYNA concentration and the decrease of dopamine turnover. Since we previously reported that high lysine diet inhibit KYNA production in the rat brain, streptozotocin-induced type I diabetes model rats were fed on 1-3% lysine added diet. The brain KYNA concentration decreased, and the dopamine turnover increased in lysine-dependent manner in the streptozotocin-induced type I diabetes model rats. Taken together with no change of KYNA precursor kynurenine's concentration, these results suggest that increase of lysine metabolite α-aminoadipic acid inhibited the KYNA synthesis from kynurenine. Present results showing inhibition of KYNA increase and induction of dopamine release by high lysine diet suggest that dietary manipulation of KYNA production can modulate dopamine release in normal rage.

锥虫代谢物kynurenic酸（Kyna）是α7烟碱乙酰胆碱受体（α7NACHR）的偏爱拮抗剂，可降低α7NACHR的封闭中多巴胺的细胞外杠杆作用。对kyna产生的激素和多巴胺能功能高赖氨酸饮食抑制大鼠大脑中的Kyna产生，链蛋白酶诱导的I型糖尿病模型大鼠在1-3％的赖氨酸上喂食，加上Braine Kyna降低了CED I型糖尿病型的大鼠。 Kyna前体kynurenine的浓度，这些结果表明，赖氨酸代谢产物α-氨基磷脂的增加抑制了Kyn，而Kyn用co虫含量抑制了kyn蛋白，而高赖氨酸饮食则通过高赖氨酸饮食而释放。