Lithium and inositol: effects on brain water homeostasis in the rat
Lithium and inositol: effects on brain water homeostasis in the rat
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DOI：
10.1007/s00213-006-0354-y
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发表时间：
2006-05-01
影响因子：
3.4
通讯作者：
Regenold, WT
中科院分区：
文献类型：
--
作者：
Phatak, P;Shaldivin, A;Regenold, WT
基本原理：自从锂最早用于精神病学以来，人们就知道它会改变体内水分的平衡。虽然锂也被认为可以降低肌醇（一种重要的脑渗透剂）的浓度，但对锂对脑水稳态的影响知之甚少。目的：确定锂是否改变脑水的稳态，如果是，其机制是否涉及肌醇浓度的变化。材料与方法：大鼠分别饲喂普通饲料或普通饲料加氯化锂11天或5周。脑被解剖，并通过湿-干法测定组织水，通过气相色谱-质谱法测定肌醇。结果如下：我们发现，与对照组大鼠（83.6 +/- 2.6%）相比，5周锂喂养大鼠（86.7 +/- 3.9%）的额叶皮质组织水平均升高3.1%，具有统计学显著性（p=0.05，校正）。在5周锂喂养大鼠的合并样本中，肌醇浓度与组织水百分比呈负相关（r=-0.50，p=0.003，校正），与对照组相比，5周锂喂养大鼠的额叶皮质和海马中肌醇浓度显著降低。喂食锂11天的大鼠在两个变量上与对照组没有显著差异。结论：这是首次报道锂诱导脑组织含水量增加。虽然其机制尚不清楚，但似乎不是由于脑肌醇浓度或血钠浓度的变化。这一发现可能对锂对大脑的治疗或毒性作用有影响，因为增加的组织水可以增强细胞的兴奋性。
Rationale: Since its earliest use in psychiatry, lithium has been known to alter body water homeostasis. Although lithium is also known to decrease the concentration of inositol, an important brain osmolyte, little is known of the effects of lithium on brain water homeostasis. Objective: To determine whether lithium alters brain water homeostasis, and, if so, whether the mechanism involves changes in inositol concentration. Materials and methods: Rats were fed regular food or regular food plus lithium chloride for either 11 days or 5 weeks. Brains were dissected and assayed for tissue water by the wet-dry method and for inositol by gas chromatography-mass spectrometry. Results: We found a statistically significant (p=0.05, corrected) 3.1% mean elevation in frontal cortex tissue water in 5-week lithium-fed rats (86.7 +/- 3.9%), compared to control rats (83.6 +/- 2.6%). Inositol concentration correlated inversely with percent tissue water (r=-0.50, p=0.003, corrected) in pooled samples of 5-week lithium-fed rats, and was significantly lower in frontal cortex and hippocampus of 5-week lithium-fed rats, compared to controls. Rats fed lithium for 11 days did not differ significantly from controls on either variable. Conclusions: This is the first report of a lithium-induced increase in brain tissue water. Although the mechanism is unclear, it does not appear to result from changes in brain inositol concentration or blood sodium concentration. This finding may have implications for the therapeutic or toxic effects of lithium on brain, because increased tissue water can augment cell excitability.