Mechanisms Of Action: Lithium And Other Antimanic Drugs

作用机制:锂和其他抗躁狂药物

基本信息

项目摘要

(1) Chronic lithium administration reduced arachidonic acid turnover in rat brain phospholipids by 80%, without affecting turnover of docosahexaenoic or palmitic acid. The brain concentration of arachidonoyl-CoA, the precursor for arachidonic acid incorporation into phospholipids, was reduced by 50%. Lithium also reduced mRNA and protein levels and enzyme activity of an arachidonate selective cytosolic phospholipase A2 (cPLA2), which releases arachidonic acid from phospholipids during receptor-mediated signal transduction. cPLA2 and the arachidonic acid cascade may be a target of lithium in the treatment of bipolar disorder. (2) Rats were chronically administered valproic acid, an anticonvulsant used to treat bipolar disorder. Arachidonic acid turnover within brain phospholipids was reduced by 30%, but cPLA2 protein was unchanged. Both valproate and lithium may act against bipolar disorder by inhibiting brain arachidonate turnover, lithium by targeting cPLA2, valproate by an as yet unknown mechanism. (3) 1H-magnetic resonance spectroscopy (MRS) showed an elevated brain myoinositol concentration in the trisomy 65Dn mouse, a model for Down syndrome (trisomy 21). A similar reduction in brain myoinositol was reported in Down syndrome. Chronic lithium treatment further reduced brain myoinositol in the mouse, consistent with a hypothesis that lithium inhibits brain inositol monophosphatase and the phosphatidylinositol cycle. (4) A mass spectrometry method was developed and used to show that turnover of myoinositol in phosphatidylinositol of cultured fetal mouse neurons was quite rapid, 10.3% per hour. The spectrometric method with an accompanying mathematical model can also quantify myoinositol turnover in the rodent brain in vivo.
(1)长期锂管理减少花生四烯酸营业额在大鼠脑磷脂80%,而不影响营业额的二十二碳六烯酸或棕榈酸。花生四烯酸结合到磷脂中的前体花生四烯酸-CoA的脑浓度降低了50%。锂还降低了花生四烯酸选择性胞质磷脂酶A2(cPLA 2)的mRNA和蛋白质水平以及酶活性,cPLA 2在受体介导的信号转导过程中从磷脂中释放花生四烯酸。cPLA 2和花生四烯酸级联反应可能是锂治疗双相情感障碍的靶点。(2)大鼠长期服用丙戊酸,一种用于治疗双相情感障碍的抗惊厥药。脑磷脂中花生四烯酸的周转率降低了30%,但cPLA 2蛋白没有变化。丙戊酸盐和锂剂均可通过抑制脑花生四烯酸转换来治疗双相情感障碍,锂剂通过靶向cPLA 2,丙戊酸盐通过一种未知的机制。(3)1H-磁共振波谱(MRS)显示,在65 Dn三体小鼠(唐氏综合征(21三体)模型)中,脑肌醇浓度升高。唐氏综合症患者的脑肌醇也有类似的减少。长期锂治疗进一步减少了小鼠的脑肌醇,这与锂抑制脑肌醇单磷酸酶和磷脂酰肌醇循环的假设一致。(4)一个质谱方法的开发和使用显示,周转肌醇磷脂酰肌醇的培养胎鼠神经元是相当迅速的,每小时10.3%。光谱方法与伴随的数学模型也可以量化肌醇营业额在啮齿动物大脑在体内。

项目成果

期刊论文数量(0)
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会议论文数量(0)
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Stanley I. Rapoport其他文献

Le métabolisme cérébral au cours du vieillissement chez le sujet sain et dans la maladie d’alzheimer
大脑新陈代谢与阿尔茨海默病的症状
  • DOI:
    10.3917/puf.lamou.1990.01.0089
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Jay S. Luxenberg;Stanley I. Rapoport
  • 通讯作者:
    Stanley I. Rapoport
RETRACTED ARTICLE: Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4
  • DOI:
    10.1186/s13024-021-00438-3
  • 发表时间:
    2021-04-16
  • 期刊:
  • 影响因子:
    17.500
  • 作者:
    Shaowei Wang;Boyang Li;Victoria Solomon;Alfred Fonteh;Stanley I. Rapoport;David A. Bennett;Zoe Arvanitakis;Helena C. Chui;Carol Miller;Patrick M. Sullivan;Hoau-Yan Wang;Hussein N. Yassine
  • 通讯作者:
    Hussein N. Yassine
RETRACTED ARTICLE: Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid Metabolites
  • DOI:
    10.1007/s11064-010-0282-4
  • 发表时间:
    2010-10-28
  • 期刊:
  • 影响因子:
    3.800
  • 作者:
    Mireille Basselin;Epolia Ramadan;Mei Chen;Stanley I. Rapoport
  • 通讯作者:
    Stanley I. Rapoport
Entry of bilirubin into the brain due to opening of the blood-brain barrier.
由于血脑屏障打开,胆红素进入大脑。
  • DOI:
  • 发表时间:
    1982
  • 期刊:
  • 影响因子:
    8
  • 作者:
    Rodney L. Levine;W. Fredericks;Stanley I. Rapoport
  • 通讯作者:
    Stanley I. Rapoport
Rapid high-affinity transport of a chemotherapeutic amino acid across the blood-brain barrier.
化疗氨基酸快速高亲和力转运穿过血脑屏障。
  • DOI:
  • 发表时间:
    1992
  • 期刊:
  • 影响因子:
    11.2
  • 作者:
    Yoshiaki Takada;D. Vistica;Nigel H. Greig;David Purdon;Stanley I. Rapoport;Quentin R. Smith
  • 通讯作者:
    Quentin R. Smith

Stanley I. Rapoport的其他文献

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{{ truncateString('Stanley I. Rapoport', 18)}}的其他基金

IMAGING DECREASED BRAIN DOCOSAHEXAENOIC ACID METABOLISM AND SIGNALING
大脑二十二碳六烯酸代谢和信号传导下降的成像
  • 批准号:
    8361447
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
CEREBROSPINAL FLUID MARKERS OF AGING AND BRAIN DISEASE
衰老和脑部疾病的脑脊液标志物
  • 批准号:
    6413958
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
DOWN SYNDROME, NEURODEVELOPMENT & NEURODEGENERATION
唐氏综合症、神经发育
  • 批准号:
    6434775
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Cerebrospinal Fluid Markers Of Aging And Brain Disease
衰老和脑疾病的脑脊液标志物
  • 批准号:
    6667885
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Mechanisms Of Action Of Lithium And Other Drugs In Bipol
锂和其他药物在 Bipol 中的作用机制
  • 批准号:
    6968662
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Brain Imaging In Human Aging, Alzheimer Disease And Rela
人类衰老、阿尔茨海默病及其相关的脑成像
  • 批准号:
    6968663
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Brain Imaging In Human Aging, Alzheimer Disease And Other Disorders
人类衰老、阿尔茨海默病和其他疾病的脑成像
  • 批准号:
    8552321
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Lipid Nutrition and the Brain
脂质营养与大脑
  • 批准号:
    8931542
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Lipids in Human Brain Disease
人脑疾病中的脂质
  • 批准号:
    8931543
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Imaging Brain Signal Transduction In Vivo With Radiolabeled Arachidonic Acid
用放射性标记的花生四烯酸对体内脑信号转导进行成像
  • 批准号:
    7963868
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

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ROLE OF CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION
细胞粘附在生物信号转导中的作用
  • 批准号:
    6238317
  • 财政年份:
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