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

Ash, Jessica A.; Velázquez, Ramón; Kelley, Christy M.; Powers, Brian E.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

doi:10.1016/j.nbd.2014.06.001

Cited by 78 publications

(140 citation statements)

References 86 publications

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“…54,55 Furthermore, poor fetal growth may result in impaired development of the septo-hippocampal circuit and its projections to the frontal cortex. [55][56][57] Morphological changes in the hippocampus may be responsible for impairment in hippocampal-related behaviours, such as learning and memory, 52 and may thus play a role in impaired cognitive development.…”

Section: Discussionmentioning

confidence: 99%

Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review

Murray

Fernandes

Fazel

et al. 2015

BJOG

234

149

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Background Neurodevelopmental disorders are increasingly believed to originate from intrauterine growth restriction (IUGR). Current reviews exploring the neurodevelopmental effects of IUGR, however, are mostly based on birthweight, an inadequate proxy. Objective We aimed to examine the association between IUGR documented in utero, and neurodevelopmental outcomes during childhood. Search strategy Medline, CINAHL, PsycInfo and Scopus were searched for relevant studies published after 1970. Selection criteria The analysis included studies that identified IUGR in utero, with follow‐up assessments between 1 month and 12 years of age. Data collection and analysis Data was extracted for cognitive, behavioural, language, motor, hearing, vision or sleep outcomes. Studies were summarised separately for children born at <35 and ≥35 weeks gestation. Main results Of 28 876 titles identified, 38 were suitable for inclusion. IUGR children born ≥35 weeks gestation scored on average 0.5 SD lower than non‐IUGR children across all neurodevelopmental assessments. IUGR children born <35 weeks of gestation scored approximately 0.7 SD lower than non‐IUGR children across all neurodevelopmental assessments. IUGR children with evidence of fetal circulatory redistribution (preferential perfusion of the brain) had more severe neurodevelopmental impairments than those born IUGR alone. Conclusions IUGR increases the risk of neurodevelopmental impairment during childhood differentially across domains. IUGR children born preterm or with evidence of fetal circulatory redistribution are more severely affected. Tweetable abstract IUGR is associated with an overall risk for neurodevelopmental delay in a range of neurodevelopmental domains.

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Section: Discussionmentioning

confidence: 99%

Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review

Murray

Fernandes

Fazel

et al. 2015

BJOG

234

149

View full text Add to dashboard Cite

show abstract

“…In this task, the animals must use extra-maze cues to locate a hidden escape platform at the end of one of the arms. Ts65Dn mice born to choline-supplemented dams exhibited lifelong improvements in spatial learning, performing nearly as well as their 2N littermates [74, 76] (Fig. 2A, B).…”

Section: Effects Of Mcs On Spatial Cognition Hippocampal Neurogenesimentioning

confidence: 98%

“…In addition to the beneficial cognitive effects of MCS in normal rats and mice, this early dietary intervention provides lasting neuroprotective effects and attenuates cognitive impairment in a wide variety of rodent disease models including aging [73, 82, 97–99], prenatal alcohol exposure [100–102], epilepsy [103–105], excitotoxicity [106, 107], Rett syndrome [108–111], and notably, DS [74–76, 112]. …”

Section: Effects Of Mcs On Spatial Cognition Hippocampal Neurogenesimentioning

confidence: 99%

Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease

Strupp

Powers²,

Velázquez³

et al. 2015

CAR

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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 DS fetuses, and include babies born to mothers unaware that they are carrying a DS fetus.

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“…Choline is an essential nutrient during fetal development due to its role in acetyl choline production, cellular membrane formation, and epigenetic regulation. MCS produced a dramatic improvement in spatial cognition in aged Ts65Dn offspring, which correlated with hippocampal neurogenesis [Velazquez et al, 2013] as well as increased density and size of basal forebrain cholinergic neurons [Ash et al, 2014]. MCS also improved attention and emotional regulation in aged Ts65Dn mice [Moon et al, 2010].…”

Section: Prenatal Diagnosis and Treatment Of Dsmentioning

confidence: 89%

Changing Paradigms in Down Syndrome: The First International Conference of the Trisomy 21 Research Society

Delabar¹,

Allinquant

Bianchi

et al. 2016

Mol Syndromol

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Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) in humans with an incidence of ∼1:1,000 live births worldwide. It is caused by the presence of an extra copy of all or a segment of the long arm of human chromosome 21 (trisomy 21). People with DS present with a constellation of phenotypic alterations involving most organs and organ systems. ID is present in all people with DS, albeit with variable severity. DS is also the most frequent genetic cause of Alzheimer's disease (AD), and ∼50% of those with DS will develop AD-related dementia. In the last few years, significant progress has been made in understanding the crucial genotype-phenotype relationships in DS, in identifying the alterations in molecular pathways leading to the various clinical conditions present in DS, and in preclinical evaluations of potential therapies to improve the overall health and well-being of individuals with DS. In June 2015, 230 scientists, advocates, patients, and family members met in Paris for the 1st International Conference of the Trisomy 21 Research Society. Here, we report some of the most relevant presentations that took place during the meeting.

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

Cited by 78 publications

References 86 publications

Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review

Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review

Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease

Changing Paradigms in Down Syndrome: The First International Conference of the Trisomy 21 Research Society

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