In offspring, an adequate maternal diet is important for neurodevelopment. One mechanism by which maternal diet impacts neurodevelopment is through its dynamic role in the development of the gut ...microbiota. Communication between the gut, and its associated microbiota, and the brain is facilitated by the vagus nerve, in addition to other routes. Currently, the mechanisms through which maternal diet impacts offspring microbiota development are not well‐defined. Therefore, this review aims to investigate the relationship between maternal diet during pregnancy and offspring microbiota development and its impact on neurodevelopment. Both human and animal model studies were reviewed to understand the impact of maternal diet on offspring microbiota development and potential consequences on neurodevelopment. In the period after birth, as reported in both human and model system studies, maternal diet impacts offspring bacterial colonization (e.g., decreased presence of Lactobacillus reuteri as a result of a high‐fat maternal diet). It remains unknown whether these changes persist into adulthood and whether they impact vulnerability to disease. Therefore, further long‐term studies are required in both human and model systems to study these changes. Our survey of the literature indicates that maternal diet influences early postnatal microbiota development, which in turn, may serve as a mechanism through which maternal diet impacts neurodevelopment.
Ischemic stroke is an unmet medical need within the clinical population and is associated with significant mortality and morbidity. Nutrition is a modifiable risk factor for ischemic stroke. A ...maternal diet that provides adequate nutrition during pregnancy and lactation is vital to the neurodevelopment of offspring. Deficiencies in nutrients during fetal growth can lead to altered early life nutritional programming, such as spina bifida, a neural tube defect. There is an opportunity for advancing therapeutic intervention by completing additional research aimed at understanding the mechanistic impact of maternal nutrition on offspring ischemic stroke. Dietary deficiencies of one‐carbon (1C) metabolites have been associated with an increased risk for stroke. 1C metabolites include folic acid and choline which play a vital role in early life neurodevelopment. Data from our laboratory demonstrates that maternal dietary deficiencies in these vitamins and nutrients impact stroke outcome in 2‐month‐old male and female offspring, however, the mechanisms through which this occurs remain unknown. The aim of the present study was to investigate the impact of maternal dietary deficiencies in folic acid or choline on neuronal viability. This project used hypoxia as an in vitro model of stroke. Prior to mating, female mice were placed on a control, folic acid, or choline deficient diet for 4 weeks. Primary neurons were isolated from embryonic tissue, grown in culture, and exposed to hypoxia, after which cells were returned to normoxia. Twenty‐four hours after hypoxia, neuronal viability and apoptosis was measured in cultures. Our results demonstrate that offspring neurons from deficient mothers had reduced cell viability. There was also a change in the level of apoptosis between maternal dietary groups and treatments. These results suggest that a maternal dietary deficiency during pregnancy negatively impacts neurons after hypoxia.
Currently, ischemic stroke is the most prevalent form of stroke compared to hemorrhagic and there is a high incidence in older adults. Nutrition is a modifiable risk factor for stroke. B-vitamins are ...part of a metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. These vitamins play an essential role in the regulation of cell proliferation, stress resistance, and embryo development. A deficiency in vitamin B12 is common in older adults and has been reported to be implicated in ischemic stroke. The aim of this review was to investigate whether vitamin B12 deficiencies impact the risk and outcome of ischemic stroke. Clinical data from our literature review strongly suggest that a deficiency in vitamin B12 is a risk factor for ischemic stroke and possible outcome. Our survey of the literature has identified that there is a gap in the understanding of the mechanisms through which a vitamin B12 deficiency leads to an increased risk of stroke and outcome. A vitamin B12 deficiency can increase homocysteine levels, which are a well-established risk factor for ischemic stroke. Another potential mechanism through which vitamin B12 deficient may impact neurological function and increase risk of stroke, is changes in myelination, however this link requires further investigation. Further studies are required in model systems to understand how a vitamin B12 deficiency changes the brain.
Folate is vital for biological processes within the body, including DNA synthesis, DNA repair, and methylation reactions that metabolize homocysteine. The role of folate is particularly important in ...pregnancy, where there is rapid cellular and tissue growth. Maternal folate deficiencies secondary to inadequate dietary supplementation are known to produce defects in the neural tube and spinal cord, yet the exact mechanism of folate in neurodevelopment is unknown. The consequences of maternal folate deficiency on offspring brain development and function beyond gestation are not well defined. The objective of this review is to investigate the role of folate deficiency in offspring neurodevelopment, and the complications that arise post-gestation. This was accomplished through a comprehensive review of the data presented in both clinical and preclinical studies. Evidence supports that folate deficiency is associated with altered offspring neurodevelopment, including smaller total brain volume, altered cortical thickness and cerebral white matter, altered neurogenesis, and neuronal apoptosis. Some of these changes have been associated with altered brain function in offspring with memory, motor function, language skills, and psychological issues. This review of literature also presents potential mechanisms of folate deficiency in neurodevelopment with altered metabolism, neuroinflammation, epigenetic modification through DNA methylation, and a genetic deficiency in one-carbon metabolism.
The global population is aging and the prevalence of age-related diseases, such as Alzheimer's disease and vascular dementia is increasing. Understanding functional impairments and disease processes ...is of vital importance in order to develop effective therapeutics. Using the natural exploratory behavior of mice, the spontaneous alternation y-maze can assess short-term spatial working memory. The protocol for y-maze testing is straightforward and requires minimal resources, as well as animal training and output. Therefore, it can be broadly applied to study short-term memory in aged rodent models.
A hemorrhagic stroke is when there a bleed in the brain, whereas an ischemic stroke is the result of blockage of blood flow to the brain, which leads to degeneration, neurotoxicity, inflammation, and ...apoptosis. ...the accompanying behavioral experience can influence the effectiveness of many potential restorative therapies. In addition to increased BDNF levels, insulin-like growth factor-1, and nerve growth factor are increased within the first 4 weeks after stroke.
Aging results in more health challenges, including neurodegeneration. Healthy aging is possible through nutrition as well as other lifestyle changes. One-carbon (1C) metabolism is a key metabolic ...network that integrates nutritional signals with several processes in the human body. Dietary supplementation of 1C components, such as folic acid, vitamin B12, and choline are reported to have beneficial effects on normal and diseased brain function. The aim of this review is to summarize the current clinical studies investigating dietary supplementation of 1C, specifically folic acid, choline, and vitamin B12, and its effects on healthy aging. Preclinical studies using model systems have been included to discuss supplementation mechanisms of action. This article will also discuss future steps to consider for supplementation. Dietary supplementation of folic acid, vitamin B12, or choline has positive effects on normal and diseased brain function. Considerations for dietary supplementation to promote healthy aging include using precision medicine for individualized plans, avoiding over-supplementation, and combining therapies.
Adequate maternal dietary levels of one-carbon metabolites, such as folic acid and choline, play an important role in the closure of the neural tube in utero; however, the impact of deficiencies in ...one-carbon (1C) metabolism on offspring neurological function after birth remain undefined. Stroke is one of the leading causes of death and disability globally. The aim of our study was to determine the impact of maternal 1C nutritional deficiencies on cerebral and peripheral blood flow after ischemic stroke in adult female offspring. In this study, female mice were placed on either control (CD)-, folic acid (FADD)-, or choline (ChDD)-deficient diets before pregnancy. Female offspring were weaned onto a CD for the duration of the study. Ischemic stroke was induced in offspring and after 6 wk cerebral and peripheral blood flow velocity was measured using ultrasound imaging. Our data showed that 11.5-mo-old female offspring from ChDD mothers had reduced blood flow in the posterior cerebral artery compared with controls. In peripheral blood flow velocity measurements, we report an aging effect. These results emphasize the importance of maternal 1C diet in early life neuro-programming on long-term vasculature health.
We demonstrate that a maternal dietary deficiency in one-carbon (1C) metabolites result in reduced cerebral blood flow in adult female offspring after ischemic stroke, but the long-term effects are not present. This result points to the key role of the maternal diet in early life neuroprogramming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.
Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterised by the progressive degeneration of dopaminergic (DA) neurons. The cause of degeneration is not well ...understood; however, both genetics and environmental factors, such as nutrition, have been implicated in the disease process. Deficiencies in one-carbon metabolism in particular have been associated with increased risk for PD onset and progression, though the precise relationship is unclear. The aim of the present review is to determine the role of one-carbon metabolism and elevated levels of homocysteine in PD onset and pathology and to identify potential mechanisms involved. A search of PubMed, Google Scholar and Web of Science was undertaken to identify relevant human and animal studies. Case-control, prospective cohort studies, meta-analyses and non-randomised trials were included in the present review. The results from human studies indicate that polymorphisms in one-carbon metabolism may increase risk for PD development. There is an unclear role for dietary B-vitamin intake on PD onset and progression. However, dietary supplementation with B-vitamins may be beneficial for PD-affected individuals, particularly those on l-DOPA (levodopa or l-3,4-dihydroxyphenylalanine) treatment. Additionally, one-carbon metabolism generates methyl groups, and methylation capacity in PD-affected individuals is reduced. This reduced capacity has an impact on expression of disease-specific genes that may be involved in PD progression. During B-vitamin deficiency, animal studies report increased vulnerability of DA cells through increased oxidative stress and altered methylation. Nutrition, especially folates and related B-vitamins, may contribute to the onset and progression of PD by making the brain more vulnerable to damage; however, further investigation is required.
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