Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.

Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.
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DOI:
10.1016/j.nbd.2014.06.001
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发表时间:
2014-10
影响因子:
6.1
通讯作者:
Strupp BJ
Strupp BJ
中科院分区:
医学1区
文献类型:
--
作者:
Ash JA;Velazquez R;Kelley CM;Powers BE;Ginsberg SD;Mufson EJ;Strupp BJ

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唐氏综合症 (DS) 的特点是智力障碍 (ID) 和早发的阿尔茨海默病 (AD) 神经病理学,包括基底前脑胆碱能神经元 (BFCN) 变性。本研究在 DS 和 AD 的 Ts65Dn 小鼠模型中验证了母体胆碱补充 (MCS) 可减轻海马功能障碍并防止 BFCN 变性的假设。在怀孕和哺乳期间,母鼠被分配给胆碱充足(1.1克/千克氯化胆碱)或补充胆碱(5.0克/千克氯化胆碱)饮食。在 13 至 17 个月大时,后代在放射臂水迷宫 (RAWM) 中进行测试,以检查空间学习和记忆,然后对 BFCN 进行无偏定量形态测量。相对于正常二体 (2N) 同窝小鼠,未补充的 Ts65Dn 小鼠的空间映射显着受损。此外,在未补充的 Ts65Dn 小鼠中还发现内侧隔膜 (MS) 海马投射 BFCN 的数量和密度显着降低。值得注意的是,MCS 显着改善了 Ts65Dn 后代中的空间映射,并增加了 MS BFCN 的数量、密度和大小。此外,MS BFCN 的密度和数量与空间记忆能力显着相关,为三体后代的 MCS 的这些行为和形态测量效应之间的功能关系提供了有力的支持。因此,怀孕期间增加母体胆碱摄入量可能是携带 DS 胎儿的准妈妈的一种安全有效的治疗方法,也是广大人群衰老过程中 BFCN 神经保护的一种可能手段。
Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer’s disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) lessens hippocampal dysfunction and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1 g/kg choline chloride) or choline supplemented (5.0 g/kg choline chloride) diet. Between 13 and 17 months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial learning and memory followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing powerful support for a functional relationship between these behavioral and morphometric effects of MCS for the trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large.
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