Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice.
Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice.
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通过对 Chrna7 无效突变小鼠的研究，补充与 α7 烟碱受体相关的妊娠期胆碱可长期改善感觉抑制。
DOI：
10.1016/j.brainres.2014.01.022
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发表时间：
2014-03-13
期刊：
影响因子：
2.9
通讯作者：
Adams, Catherine E.
中科院分区：
文献类型：
--
作者：
Stevens, Karen E.;Choo, Kevin S.;Stitzel, Jerry A.;Marks, Michael J.;Adams, Catherine E.
关键词：
围产期胆碱补充剂在啮齿动物模型中产生了几个好处，从改善学习和记忆到保护胎儿免受酒精暴露的行为影响。我们已经证明，补充胆碱通过妊娠期和哺乳期产生长期改善DBA/2小鼠的感觉抑制缺陷，其在精神分裂症患者中模拟了类似的缺陷。本研究通过向携带α7烟碱受体基因（Chrna 7）无效突变的DBA/2小鼠喂食正常或补充胆碱饮食来扩展该研究。将Chrna 7杂合子DBA/2小鼠一起繁殖。在交配时，将母鼠置于补充（5 gm/kg饲料）或正常（1.1 gm/kg饲料）胆碱组，并保持特定饲料直至后代断奶。此后，给后代喂食标准啮齿动物饲料。评估成年后代的感觉抑制。获取脑以确定海马α7烟碱受体水平。补充胆碱的Chrna 7杂合子或空突变小鼠未能显示感觉抑制的改善。只有补充野生型胆碱的小鼠仅通过降低测试振幅显示出效果的改善。这支持了补充妊娠胆碱通过α7烟碱受体改善感觉抑制的假设。尽管海马α7受体数量存在显著的基因剂量相关变化，但结合研究未显示任何海马区域中结合的任何胆碱剂量相关变化，相互作用由显著的基因型主效应驱动（野生型>杂合子>无效突变体）。这些数据与一项人类研究平行，其中在妊娠期间接受胆碱补充剂的孕妇的后代表现出比安慰剂妇女的后代更好的感觉抑制。
Perinatal choline supplementation has produced several benefits in rodent models, from improved learning and memory to protection from the behavioral effects of fetal alcohol exposure. We have shown that supplemented choline through gestation and lactation produces long-term improvement in deficient sensory inhibition in DBA/2 mice which models a similar deficit in schizophrenia patients. The present study extends that research by feeding normal or supplemented choline diets to DBA/2 mice carrying the null mutation for the α7 nicotinic receptor gene (Chrna7). DBA/2 mice heterozygotic for Chrna7 were bred together. Dams were placed on supplemented (5 gm/kg diet) or normal (1.1 gm/kg diet) choline at mating and remained on the specific diet until offspring weaning. Thereafter, offspring were fed standard rodent chow. Adult offspring were assessed for sensory inhibition. Brains were obtained to ascertain hippocampal α7 nicotinic receptor levels. Choline-supplemented mice heterozygotic or null-mutant for Chrna7 failed to show improvement in sensory inhibition. Only wildtype choline-supplemented mice showed improvement with the effect solely through a decrease in test amplitude. This supports the hypothesis that gestational-choline supplementation is acting through the α7 nicotinic receptor to improve sensory inhibition. Although there was a significant gene-dose-related change in hippocampal α7 receptor numbers, binding studies did not reveal any choline-dose-related change in binding in any hippocampal region, the interaction being driven by a significant genotype main effect (wildtype>heterozygote>null mutant). These data parallel a human study wherein the offspring of pregnant women receiving choline supplementation during gestation, showed better sensory inhibition than offspring of women on placebo.
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影响因子：
--
作者：
Leonard, S;Gault, J;Freedman, R
通讯作者：
Freedman, R
DOI：
10.1016/s0165-3806(03)00106-8
发表时间：
2003-07-12
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Adams, CE
通讯作者：
Adams, CE
影响因子：
10.6
作者：
BAKER, NJ;STAUNTON, M;FREEDMAN, R
通讯作者：
FREEDMAN, R
影响因子：
3
作者：
Gentry, C. L.;Lukas, R. J.
通讯作者：
Lukas, R. J.
影响因子：
10.6
作者：
ADLER, LE;PANG, K;ROSE, GM
通讯作者：
ROSE, GM