Chronic N-methyl-D-aspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat
Chronic N-methyl-D-aspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat
复制标题
DOI：
10.1194/jlr.m700406-jlr200
复制
发表时间：
2008-01-01
影响因子：
6.5
通讯作者：
Bazinet, Richard P.
中科院分区：
文献类型：
--
作者：
Lee, Ho-Joo;Rao, Jagadeesh S.;Bazinet, Richard P.
尽管对大鼠给予抗双相情感障碍药物可降低脑花生四烯酸周转率，但过量的N-甲基-D-天冬氨酸（NMDA）信号转导被认为有助于双相情感障碍症状，并可能增加大鼠脑磷脂中的花生四烯酸周转率。为了确定慢性NMDA是否会增加脑花生四烯酸周转，每天给大鼠施用NMDA（25 mg/kg，ip）或载体，持续21天。在未麻醉大鼠中，在第21天，静脉输注[1-C-14]花生四烯酸，并采集动脉血浆，直至动物在5分钟处以安乐死，并对其微波脑进行化学和放射性示踪剂分析。使用我们的体内脂肪酸模型的方程，我们发现与对照组相比，慢性NMDA增加了血浆未酯化花生四烯酸掺入脑磷脂的净速率（25-34%）以及脑磷脂内花生四烯酸的周转率（35-58%）。单次注射NMDA后3 h，这些变化不存在。
Whereas antibipolar drug administration to rats reduces brain arachidonic acid turnover, excessive N-methyl-D-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms and may increase arachidonic acid turnover in rat brain phospholipids. To determine whether chronic NMDA would increase brain arachidonic acid turnover, rats were daily administered NMDA (25 mg/kg, ip) or vehicle for 21 days. In un-anesthetized rats, on day 21, [1-C-14] arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was euthanized at 5 min and its microwaved brain was subjected to chemical and radio-tracer analysis. Using equations from our in vivo fatty acid model, we found that compared with controls, chronic NMDA increased the net rate of incorporation of plasma unesterified arachidonic acid into brain phospholipids (25-34%) as well as the turnover of arachidonic acid within brain phospholipids (35-58%). These changes were absent at 3 h after a single NMDA injection.