Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline.
Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline.
复制标题
围产期胆碱增加可永久改善 DBA/2 小鼠的感觉抑制缺陷。
DOI：
10.1007/s00213-008-1170-3
复制
发表时间：
2008
影响因子：
3.4
通讯作者：
Kisley,MichaelA
中科院分区：
文献类型：
--
作者：
Stevens,KarenE;Adams,CatherineE;Yonchek,Joan;Hickel,Cindy;Danielson,Jeffrey;Kisley,MichaelA
基本原理精神分裂症患者和某些近交小鼠品系（即 DBA/2）表现出感觉抑制缺陷，这与海马 α7 烟碱受体数量减少以及 α7 基因启动子区域的潜在多态性有关。妊娠期间增加母体膳食胆碱（一种选择性 α7 激动剂）已被证明会对成年后代行为产生长期变化（即改善大鼠的学习和记忆）。目的本研究的目的是通过母体胆碱补充改善 DBA/2 小鼠的感觉抑制。材料和方法 DBA/2 母鼠在整个过程中接受正常（1.1 g/kg）或补充胆碱（5 g/kg）饮食妊娠和哺乳期。后代在断奶时接受正常饮食，并在成年时评估感觉抑制参数。比较了对相同配对听觉刺激的诱发脑电图反应。研究结束时，收集大脑进行放射自显影评估海马α-金环蛇毒素结合水平，以可视化α7烟碱受体。结果与正常胆碱饮食妊娠的小鼠相比，在妊娠期间补充胆碱的后代小鼠表现出明显改善的感觉抑制。这种改善是由于对第二个刺激的反应显着减少而产生的，表明对该刺激的抑制得到了改善。海马 CA1 和齿状回区域的 α7 受体数量同时增加，表明这种增加可能是抑制作用改善的原因。结论这些数据表明，妊娠期补充胆碱可永久改善与精神分裂症相关的缺陷，并可能对人类产前营养产生影响。
RationaleSchizophrenia patients and certain inbred mouse strains (i.e., DBA/2) show deficient sensory inhibition which has been linked to reduced numbers of hippocampal α7 nicotinic receptors and to underlying polymorphisms in the promoter region for the α7 gene. Increasing maternal dietary choline, a selective α7 agonist, during gestation has been shown to produce long-term changes in adult offspring behavior (i.e., improved learning and memory in rats).ObjectivesThe objective of this study is to improve sensory inhibition in DBA/2 mice through maternal choline supplementation.Materials and methodsDBA/2 dams were placed on normal (1.1 g/kg) or supplemented (5 g/kg) choline diet throughout gestation and lactation. Offspring were placed on normal diet at weaning and were assessed for sensory inhibition parameters at adulthood. Evoked EEG responses to identical paired auditory stimuli were compared. At the end of the study, the brains were collected for autoradiographic assessment of hippocampal levels of α-bungarotoxin binding to visualize α7 nicotinic receptors.ResultsOffspring mice which were choline supplemented during gestation showed significantly improved sensory inhibition compared to mice gestated on the normal choline diet. The improvement was produced by a significant reduction in the response to the second stimulus, demonstrating improved inhibition to that stimulus. There was a concurrent increase in α7 receptor numbers in both the CA1 and dentate gyrus regions of the hippocampus suggesting that this increase may be responsible for the improved inhibition.ConclusionsThese data show that gestational choline supplementation produces permanent improvement in a deficit associated with schizophrenia and may have implications for human prenatal nutrition.