The common inositol-reversible effect of mood stabilizers on neurons does not involve GSK3 inhibition, myo-inositol-1-phosphate synthase or the sodium-dependent myo-inositol transporters

被引：31

作者：

Di Daniel, Elena

Cheng, Lili

Maycox, Peter R.

Mudge, Anne W.

机构：

[1] GlaxoSmithKline, Schizophrenia & Bipolar Neurophysiol & Pharmacol, Psychiat Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England

[2] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England

[3] UCL, Dept Physiol, London WC1E 6BT, England

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2006年 / 32卷 / 1-2期

关键词：

sensory neurons; GSK3; phosphoinositide signaling; lithium; valprote; carbamazepine; inositol; transporters; MIP-synthese;

D O I：

10.1016/j.mcn.2006.01.015

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We previously showed that the mood stabilizers lithium, valproate (VPA), and carbamazepine (CBZ) have a common, inositol-reversible effect on the dynamic behavior of sensory neurons, suggesting that they all inhibit phosphoinositide (PIns) synthesis. We now report similar effects of the drugs in cortical neurons and show by mRNA analysis that these neurons do not express myo-inositol-1-phosphate synthase (MIP-synthase) or the sodium-dependent myo-inositol transporters (SMIT1 and SMIT2), but they do express the H+/myo-inositol transporter (HMIT) mRNA and protein. We used glycogen synthase kinase-3 (GSK3) inhibitors and Western blotting of GSK3 targets to confirm that the common effects of the drugs on both sensory and cortical neuron growth cones are inositol-dependent and GSK3-independent. Moreover, the anti-convulsant drugs gabapentin and phenytoin do not mimic the mood stabilizers. These results confirm that the common inositol-reversible effect of mood stabilizers on neurons does not involve GSK3 and further show that the effects are independent of MIP-synthase and SMIT transporters. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：27 / 36

页数：10

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