scholarly journals Maternal Choline Supplementation as a Potential Therapy for Down Syndrome: Assessment of Effects Throughout the Lifespan

2021 ◽  
Vol 13 ◽  
Author(s):  
Brian E. Powers ◽  
Ramon Velazquez ◽  
Myla S. Strawderman ◽  
Stephen D. Ginsberg ◽  
Elliott J. Mufson ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Maternal Diet ◽  
Ts65dn Mouse ◽  
Attentional Function ◽  
Beneficial Effects ◽  
Affective Functioning ◽  
Pregnancy And Lactation ◽  
Essential Nutrient ◽  
Choline Intake ◽  
Cognitive Benefit

Maternal choline supplementation (MCS) has emerged as a promising therapy to lessen the cognitive and affective dysfunction associated with Down syndrome (DS). Choline is an essential nutrient, especially important during pregnancy due to its wide-ranging ontogenetic roles. Using the Ts65Dn mouse model of DS, our group has demonstrated that supplementing the maternal diet with additional choline (4-5 × standard levels) during pregnancy and lactation improves spatial cognition, attention, and emotion regulation in the adult offspring. The behavioral benefits were associated with a rescue of septohippocampal circuit atrophy. These results have been replicated across a series of independent studies, although the magnitude of the cognitive benefit has varied. We hypothesized that this was due, at least in part, to differences in the age of the subjects at the time of testing. Here, we present new data that compares the effects of MCS on the attentional function of adult Ts65Dn offspring, which began testing at two different ages (6 vs. 12 months of age). These data replicate and extend the results of our previous reports, showing a clear pattern indicating that MCS has beneficial effects in Ts65Dn offspring throughout life, but that the magnitude of the benefit (relative to non-supplemented offspring) diminishes with aging, possibly because of the onset of Alzheimer's disease-like neuropathology. In light of growing evidence that increased maternal choline intake during pregnancy is beneficial to the cognitive and affective functioning of all offspring (e.g., neurotypical and DS), the addition of this nutrient to a prenatal vitamin regimen would be predicted to have population-wide benefits and provide early intervention for fetuses with DS, notably including babies born to mothers unaware that they are carrying a fetus with DS.

scholarly journals Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome

2015 ◽  
Vol 221 (9) ◽  
pp. 4337-4352 ◽  
Author(s):  
Brian E. Powers ◽  
Ramon Velazquez ◽  
Christy M. Kelley ◽  
Jessica A. Ash ◽  
Myla S. Strawderman ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Basal Forebrain ◽  
Cholinergic Neuron ◽  
Ts65dn Mouse ◽  
Neuron Morphology ◽  
Attentional Function ◽  
Basal Forebrain Cholinergic Neuron

scholarly journals Lithium Restores Neurogenesis in the Subventricular Zone of the Ts65Dn Mouse, a Model for Down Syndrome

2010 ◽  
Vol 20 (1) ◽  
pp. 106-118 ◽  
Author(s):  
Patrizia Bianchi ◽  
Elisabetta Ciani ◽  
Andrea Contestabile ◽  
Sandra Guidi ◽  
Renata Bartesaghi
Keyword(s):  
Down Syndrome ◽  
Subventricular Zone ◽  
Ts65dn Mouse

Sucrose feeding during pregnancy and lactation elicits distinct metabolic response in offspring of an inbred genetic model of metabolic syndrome

2007 ◽  
Vol 292 (5) ◽  
pp. E1318-E1324 ◽  
Author(s):  
Lucie Šedová ◽  
Ondřej Šeda ◽  
Ludmila Kazdová ◽  
Blanka Chylíková ◽  
Pavel Hamet ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Genetic Model ◽  
Metabolic Response ◽  
Maternal Diet ◽  
Later Life ◽  
Standard Diet ◽  
Lipoprotein Subfractions ◽  
Sucrose Feeding ◽  
Pregnancy And Lactation

The importance of early environment, including maternal diet during pregnancy, is suspected to play a major role in pathogenesis of metabolic syndrome and related conditions. One of the proposed mechanisms is a mismatch between the prenatal and postnatal environments, leading to misprogramming of the metabolic and signaling pathways of the developing fetus. We assessed whether the exposure to high-sucrose diet (HSD) alleviates the detrimental effects of sucrose feeding in later life (predictive adaptive hypothesis) in a highly inbred model of metabolic syndrome, the PD/Cub rat. Rat dams were continuously fed either standard or HSD (70% calories as sucrose) starting 1 wk before breeding, throughout pregnancy, at birth, and until weaning of the offspring. After weaning, all male offspring were fed HSD until the age of 20 wk, when detailed metabolic and morphometric profiles were ascertained. The early life exposure to a sucrose-rich diet resulted in distinct responses to longtime postnatal HSD feeding. Offspring of the sucrose-fed mothers displayed higher adiposity and substantial increases in triglyceride liver content together with unfavorable distribution of cholesterol into lipoprotein subfractions. On the other hand, their adiponectin concentrations were significantly higher, and insulin sensitivity of skeletal muscle was enhanced compared with the offspring of standard diet-fed mothers. Triglycerides, free fatty acids, overall glucose tolerance, and the insulin sensitivity of adipose tissue were comparable in both groups. In the genetically identical animals, maternal HSD feeding elicited a variety of subtle effects but did not lead to predictive adaptive protection from most HSD-induced metabolic derangements.

scholarly journals The effect of maternal and post-weaning low and high glycaemic index diets on glucose tolerance, fat deposition and hepatic function in rat offspring

2015 ◽  
Vol 7 (3) ◽  
pp. 320-329 ◽  
Author(s):  
J. Gugusheff ◽  
P. Sim ◽  
A. Kheng ◽  
S. Gentili ◽  
M. Al-Nussairawi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Later Life ◽  
Hepatic Function ◽  
Female Offspring ◽  
Glycaemic Index ◽  
Visceral Adiposity ◽  
Beneficial Effects ◽  
Pregnancy And Lactation ◽  
Total Body ◽  
The Impact

Clinical studies have reported beneficial effects of a maternal low glycaemic index (GI) diet on pregnancy and neonatal outcomes, but the impact of the diet on the offspring in later life, and the mechanisms underlying these effects, remain unclear. In this study, Albino Wistar rats were fed either a low GI (n=14) or high GI (n=14) diet during pregnancy and lactation and their offspring weaned onto either the low or high GI diet. Low GI dams had better glucose tolerance (AUC[glucose], 1322±55 v. 1523±72 mmol min/l, P<0.05) and a lower proportion of visceral fat (19.0±2.9 v. 21.7±3.8% of total body fat, P<0.05) compared to high GI dams. Female offspring of low GI dams had lower visceral adiposity (0.45±0.03 v. 0.53±0.03% body weight, P<0.05) and higher glucose tolerance (AUC[glucose], 1243±29 v. 1351±39 mmol min/l, P<0.05) at weaning, as well as lower hepatic PI3K-p85 mRNA at 12 weeks of age. No differences in glucose tolerance or hepatic gene expression were observed in male offspring, but the male low GI offspring did have reduced hepatic lipid content at weaning. These findings suggest that consuming a low GI diet during pregnancy and lactation can improve glucose tolerance and reduce visceral adiposity in the female offspring at weaning, and may potentially produce long-term reductions in the hepatic lipogenic capacity of these offspring.

Of mice and Down syndrome

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 472-472 ◽  
Author(s):  
Jeffrey W. Taub
Keyword(s):  
Down Syndrome ◽  
Human Chromosome ◽  
Chromosome 21 ◽  
Ts65dn Mouse ◽  
Human Chromosome 21 ◽  
Shed Light

Analyzing hematopoiesis in the Ts65Dn mouse, which is trisomic for many orthologs of human chromosome 21 genes, may shed light on leukemogenesis in Down syndrome, as demonstrated by Kirsammer and colleagues in this issue.

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