Strupp Barbara J, Powers Brian E, Velazquez Ramon, Ash Jessica A, Kelley Christy M, Alldred Melissa J, Strawderman Myla, Caudill Marie A, Mufson Elliott J, Ginsberg Stephen D
Division of Nutritional Sciences and Department of Psychology, Cornell University, Ithaca, NY, USA.
Curr Alzheimer Res. 2016;13(1):97-106. doi: 10.2174/1567205012666150921100311.
Although Down syndrome (DS) can be diagnosed prenatally, currently there are no effective treatments to lessen the intellectual disability (ID) which is a hallmark of this disorder. Furthermore, starting as early as the third decade of life, DS individuals exhibit the neuropathological hallmarks of Alzheimer's disease (AD) with subsequent dementia, adding substantial emotional and financial burden to their families and society at large. A potential therapeutic strategy emerging from the study of trisomic mouse models of DS is to supplement the maternal diet with additional choline during pregnancy and lactation. Studies demonstrate that maternal choline supplementation (MCS) markedly improves spatial cognition and attentional function, as well as normalizes adult hippocampal neurogenesis and offers protection to basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model of DS. These effects on neurogenesis and BFCNs correlate significantly with spatial cognition, suggesting functional relationships. In this review, we highlight some of these provocative findings, which suggest that supplementing the maternal diet with additional choline may serve as an effective and safe prenatal strategy for improving cognitive, affective, and neural functioning in DS. In light of growing evidence that all pregnancies would benefit from increased maternal choline intake, this type of recommendation could be given to all pregnant women, thereby providing a very early intervention for individuals with DS, and include babies born to mothers unaware that they are carrying a fetus with DS.
尽管唐氏综合征(DS)可在产前诊断出来,但目前尚无有效的治疗方法来减轻该疾病标志性的智力残疾(ID)。此外,早在生命的第三个十年,DS患者就会出现阿尔茨海默病(AD)的神经病理学特征,随后发展为痴呆症,给其家庭和整个社会带来了巨大的情感和经济负担。从DS三体小鼠模型研究中出现的一种潜在治疗策略是在怀孕和哺乳期给母体饮食补充额外的胆碱。研究表明,母体补充胆碱(MCS)可显著改善空间认知和注意力功能,使成年海马神经发生正常化,并为DS的Ts65Dn小鼠模型中的基底前脑胆碱能神经元(BFCN)提供保护。这些对神经发生和BFCN的影响与空间认知显著相关,表明存在功能关系。在这篇综述中,我们强调了一些引人注目的发现,这些发现表明给母体饮食补充额外的胆碱可能是一种有效且安全的产前策略,用于改善DS患者认知、情感和神经功能。鉴于越来越多的证据表明所有孕妇都将从增加母体胆碱摄入量中受益,这种建议可以提供给所有孕妇,从而为DS患者提供非常早期的干预,包括那些母亲在不知情的情况下怀有DS胎儿所生的婴儿。