Maternal choline supplementation in a mouse model of Down syndrome: Effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring.
Maternal choline supplementation in a mouse model of Down syndrome: Effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring.
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DOI：
10.1016/j.neuroscience.2016.11.001
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发表时间：
2017-01-06
期刊：
影响因子：
3.3
通讯作者：
Strupp BJ
中科院分区：
文献类型：
--
作者：
Powers BE;Kelley CM;Velazquez R;Ash JA;Strawderman MS;Alldred MJ;Ginsberg SD;Mufson EJ;Strupp BJ
唐氏综合征（DS）和阿尔茨海默病（AD）的Ts 65 Dn小鼠模型表现出认知障碍和基底前脑胆碱能神经元（BFCN）的变性。我们以前的研究表明，母亲胆碱补充剂（MCS）提高注意力和空间认知在Ts 65 Dn后代，正常化海马神经发生，并减少内侧隔核（MSN）的BFCN变性。在这里，我们确定了（i）BFCN变性是否有助于注意力功能障碍，以及（ii）围产期MCS的注意力益处是否是由于BFCN形态的变化。Ts 65 Dn母鼠在妊娠期和哺乳期喂食补充胆碱或标准饮食。Ts 65 Dn和二体（2N）对照后代作为成年人（12-17月龄）进行了一系列操作性注意力任务的测试，然后进行BFCN的形态测量评估。Ts 65 Dn小鼠表现出相对于2N小鼠的学习和注意力受损，MCS在两种基因型中显着改善了这些功能。我们还发现，第一次，在Meynert/无名质（NBM/SI）的基底核BFCN的数量显着增加，在Ts 65 Dn小鼠相对于对照组。相反，MSN中BFCN的数量显著减少。另一个新的发现是，在Ts 65 Dn小鼠的两个基底前脑区域的BFCN的体积显着更大。MCS未使NBM/SI或MSN中的任何这些形态学异常正常化。最后，相关分析显示，注意绩效与BFCN体积呈负相关，与BFCN密度呈正相关。这些结果支持MCS对Ts 65 Dn和2N后代的终身注意力益处，并对AD中的人类DS和病理学衰减的翻译具有深远的影响。
The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer’s disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hippocampal neurogenesis, and lessens BFCN degeneration in the medial septal nucleus (MSN). Here we determined whether (i) BFCN degeneration contributes to attentional dysfunction, and (ii) whether the attentional benefits of perinatal MCS are due to changes in BFCN morphology. Ts65Dn dams were fed either a choline-supplemented or standard diet during pregnancy and lactation. Ts65Dn and disomic (2N) control offspring were tested as adults (12–17 months of age) on a series of operant attention tasks, followed by morphometric assessment of BFCNs. Ts65Dn mice demonstrated impaired learning and attention relative to 2N mice, and MCS significantly improved these functions in both genotypes. We also found, for the first time, that the number of BFCNs in the nucleus basalis of Meynert/substantia innominata (NBM/SI) was significantly increased in Ts65Dn mice relative to controls. In contrast, the number of BFCNs in the MSN was significantly decreased. Another novel finding was that the volume of BFCNs in both basal forebrain regions was significantly larger in Ts65Dn mice. MCS did not normalize any of these morphological abnormalities in the NBM/SI or MSN. Finally, correlational analysis revealed that attentional performance was inversely associated with BFCN volume, and positively associated with BFCN density. These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD.
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影响因子：
2.5
作者：
Alldred, Melissa J.;Lee, Sang Han;Ginsberg, Stephen D.
通讯作者：
Ginsberg, Stephen D.
影响因子：
2
作者：
Gundersen, HJG;Jensen, EBV;Nielsen, J
通讯作者：
Nielsen, J
DOI：
10.1073/pnas.93.23.13333
发表时间：
1996-11-12
影响因子：
11.1
作者：
Holtzman, DM;Santucci, D;Mobley, WC
通讯作者：
Mobley, WC
影响因子：
6.1
作者：
Ash JA;Velazquez R;Kelley CM;Powers BE;Ginsberg SD;Mufson EJ;Strupp BJ
通讯作者：
Strupp BJ
影响因子：
2
作者：
Cheng, Ruey-Kuang;MacDonald, Christopher J.;Meck, Warren H.
通讯作者：
Meck, Warren H.