Abstract
Maternal hyperhomocysteinemia (hHcy) induced by a high methionine diet delays brain maturation and leads to impairment of learning performance in the offspring. Because methionine-homocysteine metabolism is related to the regulation of gene expression through one-carbon metabolism, we investigated whether maternal supplementation with methionine affects the expression of Adam10, Bace1, Bace2, Ps1, Ps2, Tace, App, Il-1E, Il-1β and Tnf-α, genes related to Alzheimer’s disease (AD) risk, in the offspring. Thirteen female mice were distributed into the following groups: a) standard diet and b) standard diet supplemented with 1% methionine in water. After birth, the offspring were organized into Control (CT) and Supplemented Diet (SD) groups, and at Postnatal Day (PND) 90, all animals were weighed and then euthanized. The homocysteine (Hcy) concentration in plasma was measured, and the whole brain was weighed and dissected, and the hippocampus used for gene expression analyses. A decrease in total body weight was found in SD group, but no differences in brain weight were observed. The maternal diet did not seem to affect the Hcy concentration of PND 90 offspring. No differences were found in the expression of AD related genes in the hippocampus (p>0.05). In conclusion, hHcy induced by methionine supplementation during pregnancy and lactation did not affect the expression of genes related to AD risk in the offspring.
Highlights
Gestational programming is defined as a process whereby a stimulus or a stress, occurring in a critical period of development, can permanently change the structure, physiology, and metabolism of the offspring, predisposing individuals to disease in adult life [1]
No differences were found in the expression of the following genes related to AD risk in the hippocampus (Table 3): Adam10 (t(12)=-0.07, p=0.94), Bace1(t(12)= -0.01, p=0.99), Bace2 (t(12)= 0.06, p=0.95), Ps1 (t(12)= -0.15, p=0.90), Ps2 (t(12)= 0.02, p=0.98), Tace (t(12)= 0.13, p=0.90), App (t(12)= -0.09, p=0.92), Il-1α (t(12)=0.01, p=0.99), Il-1β (t(12)=-0.25, p=0.80) and Tnf-α (t(11)=-0.05, p=0.96)
This research effort has been motivated by the recognition of the influence maternal nutrition has on fetal programming and by the fact that its consequences generally arise later in life [25]
Summary
Gestational programming is defined as a process whereby a stimulus or a stress, occurring in a critical period of development, can permanently change the structure, physiology, and metabolism of the offspring, predisposing individuals to disease in adult life [1]. Maternal nutrition during pregnancy plays a key role in the growth of the fetus and placenta, and experimental studies in animals have shown that parental diet can impair fetal health through changes in DNA methylation patterns [3]. This process is one of the epigenetic mechanisms that regulate gene expression and is sensitive to one-carbon metabolism, which is influenced by the methionine-homocysteine flow. Hcy concentration may vary considerably among individuals according to genetic, dietary and environmental factors, and elevated plasma concentrations have been identified as a risk factor for a wide range of pathological conditions [6] such as cardiovascular disease [7,8] and AD [9,10]
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