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Article ; Online: Epigenetics, Nutrition, and the Brain: Improving Mental Health through Diet.

Bekdash, Rola A

International journal of molecular sciences

2024 Volume 25, Issue 7

Abstract: The relationship between nutrition and brain health is intricate. Studies suggest that nutrients during early life impact not only human physiology but also mental health. Although the exact molecular mechanisms that depict this relationship remain ... ...

Abstract	The relationship between nutrition and brain health is intricate. Studies suggest that nutrients during early life impact not only human physiology but also mental health. Although the exact molecular mechanisms that depict this relationship remain unclear, there are indications that environmental factors such as eating, lifestyle habits, stress, and physical activity, influence our genes and modulate their function by epigenetic mechanisms to shape mental health outcomes. Epigenetic mechanisms act as crucial link between genes and environmental influences, proving that non-genetic factors could have enduring effects on the epigenome and influence health trajectories. We review studies that demonstrated an epigenetic mechanism of action of nutrition on mental health, focusing on the role of specific micronutrients during critical stages of brain development. The methyl-donor micronutrients of the one-carbon metabolism, such as choline, betaine, methionine, folic acid, VitB6 and VitB12 play critical roles in various physiological processes, including DNA and histone methylation. These micronutrients have been shown to alter gene function and susceptibility to diseases including mental health and metabolic disorders. Understanding how micronutrients influence metabolic genes in humans can lead to the implementation of early nutritional interventions to reduce the risk of developing metabolic and mental health disorders later in life.
MeSH term(s)	Humans ; Mental Health ; Diet ; Brain ; Epigenesis, Genetic ; Micronutrients
Chemical Substances	Micronutrients
Language	English
Publishing date	2024-04-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25074036
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Methyl Donors, Epigenetic Alterations, and Brain Health: Understanding the Connection.

Bekdash, Rola A

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Methyl donors such as choline, betaine, folic acid, methionine, and vitamins B6 and B12 are critical players in the one-carbon metabolism and have neuroprotective functions. The one-carbon metabolism comprises a series of interconnected chemical pathways ...

Abstract	Methyl donors such as choline, betaine, folic acid, methionine, and vitamins B6 and B12 are critical players in the one-carbon metabolism and have neuroprotective functions. The one-carbon metabolism comprises a series of interconnected chemical pathways that are important for normal cellular functions. Among these pathways are those of the methionine and folate cycles, which contribute to the formation of S-adenosylmethionine (SAM). SAM is the universal methyl donor of methylation reactions such as histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and play roles in human health and disease. Epigenetic mechanisms have been considered a bridge between the effects of environmental factors, such as nutrition, and phenotype. Studies in human and animal models have indicated the importance of the optimal levels of methyl donors on brain health and behavior across the lifespan. Imbalances in the levels of these micronutrients during critical periods of brain development have been linked to epigenetic alterations in the expression of genes that regulate normal brain function. We present studies that support the link between imbalances in the levels of methyl donors, epigenetic alterations, and stress-related disorders. Appropriate levels of these micronutrients should then be monitored at all stages of development for a healthier brain.
MeSH term(s)	Animals ; Humans ; Diet ; S-Adenosylmethionine/metabolism ; Methionine/metabolism ; DNA Methylation ; Epigenesis, Genetic ; Folic Acid/metabolism ; Brain/metabolism ; Micronutrients/metabolism ; Carbon/metabolism
Chemical Substances	S-Adenosylmethionine (7LP2MPO46S) ; Methionine (AE28F7PNPL) ; Folic Acid (935E97BOY8) ; Micronutrients ; Carbon (7440-44-0)
Language	English
Publishing date	2023-01-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032346
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Article ; Online: Methyl Donors, Epigenetic Alterations, and Brain Health

Rola A. Bekdash

International Journal of Molecular Sciences, Vol 24, Iss 2346, p

Understanding the Connection

2023 Volume 2346

Abstract	Methyl donors such as choline, betaine, folic acid, methionine, and vitamins B6 and B12 are critical players in the one-carbon metabolism and have neuroprotective functions. The one-carbon metabolism comprises a series of interconnected chemical pathways that are important for normal cellular functions. Among these pathways are those of the methionine and folate cycles, which contribute to the formation of S-adenosylmethionine (SAM). SAM is the universal methyl donor of methylation reactions such as histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and play roles in human health and disease. Epigenetic mechanisms have been considered a bridge between the effects of environmental factors, such as nutrition, and phenotype. Studies in human and animal models have indicated the importance of the optimal levels of methyl donors on brain health and behavior across the lifespan. Imbalances in the levels of these micronutrients during critical periods of brain development have been linked to epigenetic alterations in the expression of genes that regulate normal brain function. We present studies that support the link between imbalances in the levels of methyl donors, epigenetic alterations, and stress-related disorders. Appropriate levels of these micronutrients should then be monitored at all stages of development for a healthier brain.
Keywords	brain ; epigenetics ; methyl donors ; SAM ; stress ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Cholinergic System, the Adrenergic System and the Neuropathology of Alzheimer's Disease.

Bekdash, Rola A

International journal of molecular sciences

2021 Volume 22, Issue 3

Abstract: Neurodegenerative diseases are a major public health problem worldwide with a wide spectrum of symptoms and physiological effects. It has been long reported that the dysregulation of the cholinergic system and the adrenergic system are linked to the ... ...

Abstract	Neurodegenerative diseases are a major public health problem worldwide with a wide spectrum of symptoms and physiological effects. It has been long reported that the dysregulation of the cholinergic system and the adrenergic system are linked to the etiology of Alzheimer's disease. Cholinergic neurons are widely distributed in brain regions that play a role in cognitive functions and normal cholinergic signaling related to learning and memory is dependent on acetylcholine. The Locus Coeruleus norepinephrine (LC-NE) is the main noradrenergic nucleus that projects and supplies norepinephrine to different brain regions. Norepinephrine has been shown to be neuroprotective against neurodegeneration and plays a role in behavior and cognition. Cholinergic and adrenergic signaling are dysregulated in Alzheimer's disease. The degeneration of cholinergic neurons in nucleus basalis of Meynert in the basal forebrain and the degeneration of LC-NE neurons were reported in Alzheimer's disease. The aim of this review is to describe current literature on the role of the cholinergic system and the adrenergic system (LC-NE) in the pathology of Alzheimer's disease and potential therapeutic implications.
MeSH term(s)	Acetylcholine/metabolism ; Adrenergic Neurons/metabolism ; Adrenergic Neurons/pathology ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Animals ; Basal Nucleus of Meynert/metabolism ; Basal Nucleus of Meynert/pathology ; Cholinergic Neurons/metabolism ; Cholinergic Neurons/pathology ; Disease Models, Animal ; Gene Expression Regulation ; Hippocampus/metabolism ; Hippocampus/pathology ; Humans ; Locus Coeruleus/metabolism ; Locus Coeruleus/pathology ; Memory/physiology ; Norepinephrine/metabolism ; Receptors, Muscarinic/genetics ; Receptors, Muscarinic/metabolism ; Receptors, Nicotinic/genetics ; Receptors, Nicotinic/metabolism ; Signal Transduction
Chemical Substances	Receptors, Muscarinic ; Receptors, Nicotinic ; Acetylcholine (N9YNS0M02X) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2021-01-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22031273
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Article ; Online: Early Life Nutrition and Mental Health: The Role of DNA Methylation.

Bekdash, Rola A

Nutrients

2021 Volume 13, Issue 9

Abstract: Does the quality of our diet during early life impact our long-term mental health? Accumulating evidence suggests that nutrition interacts with our genes and that there is a strong association between the quality of diet and mental health throughout life. ...

Abstract	Does the quality of our diet during early life impact our long-term mental health? Accumulating evidence suggests that nutrition interacts with our genes and that there is a strong association between the quality of diet and mental health throughout life. Environmental influences such as maternal diet during pregnancy or offspring diet have been shown to cause epigenetic changes during critical periods of development, such as chemical modifications of DNA or histones by methylation for the regulation of gene expression. One-carbon metabolism, which consists of the folate and methionine cycles, is influenced by the diet and generates S-Adenosylmethinoine (SAM), the main methyl donor for methylation reactions such as DNA and histone methylation. This review provides current knowledge on how the levels of one-carbon metabolism associated micronutrients such as choline, betaine, folate, methionine and B vitamins that play a role in brain function can impact our well-being and mental health across the lifespan. Micronutrients that act as methyl donors for SAM formation could affect global or gene methylation, altering gene expression and phenotype. Strategies should then be adopted to better understand how these nutrients work and their impact at different stages of development to provide individualized dietary recommendations for better mental health outcomes.
MeSH term(s)	DNA Methylation ; Female ; Humans ; Infant ; Infant Nutritional Physiological Phenomena/physiology ; Maternal Nutritional Physiological Phenomena/physiology ; Mental Disorders/etiology
Language	English
Publishing date	2021-09-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13093111
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Article ; Online: The Cholinergic System, the Adrenergic System and the Neuropathology of Alzheimer’s Disease

Rola A. Bekdash

International Journal of Molecular Sciences, Vol 22, Iss 3, p

2021 Volume 1273

Abstract	Neurodegenerative diseases are a major public health problem worldwide with a wide spectrum of symptoms and physiological effects. It has been long reported that the dysregulation of the cholinergic system and the adrenergic system are linked to the etiology of Alzheimer’s disease. Cholinergic neurons are widely distributed in brain regions that play a role in cognitive functions and normal cholinergic signaling related to learning and memory is dependent on acetylcholine. The Locus Coeruleus norepinephrine (LC-NE) is the main noradrenergic nucleus that projects and supplies norepinephrine to different brain regions. Norepinephrine has been shown to be neuroprotective against neurodegeneration and plays a role in behavior and cognition. Cholinergic and adrenergic signaling are dysregulated in Alzheimer’s disease. The degeneration of cholinergic neurons in nucleus basalis of Meynert in the basal forebrain and the degeneration of LC-NE neurons were reported in Alzheimer’s disease. The aim of this review is to describe current literature on the role of the cholinergic system and the adrenergic system (LC-NE) in the pathology of Alzheimer’s disease and potential therapeutic implications.
Keywords	acetylcholine ; adrenergic ; Alzheimer ; cholinergic ; cognition ; epigenetics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Early Life Nutrition and Mental Health: The Role of DNA Methylation

Bekdash, Rola A

Nutrients. 2021 Sept. 04, v. 13, no. 9

2021

Abstract	Does the quality of our diet during early life impact our long-term mental health? Accumulating evidence suggests that nutrition interacts with our genes and that there is a strong association between the quality of diet and mental health throughout life. Environmental influences such as maternal diet during pregnancy or offspring diet have been shown to cause epigenetic changes during critical periods of development, such as chemical modifications of DNA or histones by methylation for the regulation of gene expression. One-carbon metabolism, which consists of the folate and methionine cycles, is influenced by the diet and generates S-Adenosylmethinoine (SAM), the main methyl donor for methylation reactions such as DNA and histone methylation. This review provides current knowledge on how the levels of one-carbon metabolism associated micronutrients such as choline, betaine, folate, methionine and B vitamins that play a role in brain function can impact our well-being and mental health across the lifespan. Micronutrients that act as methyl donors for SAM formation could affect global or gene methylation, altering gene expression and phenotype. Strategies should then be adopted to better understand how these nutrients work and their impact at different stages of development to provide individualized dietary recommendations for better mental health outcomes.
Keywords	DNA ; DNA methylation ; betaine ; brain ; choline ; diet ; epigenetics ; folic acid ; gene expression ; gene expression regulation ; genes ; histones ; longevity ; maternal nutrition ; mental health ; metabolism ; methionine ; phenotype ; pregnancy ; progeny
Language	English
Dates of publication	2021-0904
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13093111
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Neuroprotective Effects of Choline and Other Methyl Donors.

Bekdash, Rola A

Nutrients

2019 Volume 11, Issue 12

Abstract: Recent evidence suggests that physical and mental health are influenced by an intricate interaction between genes and environment. Environmental factors have been shown to modulate neuronal gene expression and function by epigenetic mechanisms. Exposure ... ...

Abstract	Recent evidence suggests that physical and mental health are influenced by an intricate interaction between genes and environment. Environmental factors have been shown to modulate neuronal gene expression and function by epigenetic mechanisms. Exposure to these factors including nutrients during sensitive periods of life could program brain development and have long-lasting effects on mental health. Studies have shown that early nutritional intervention that includes methyl-donors improves cognitive functions throughout life. Choline is a micronutrient and a methyl donor that is required for normal brain growth and development. It plays a pivotal role in maintaining structural and functional integrity of cellular membranes. It also regulates cholinergic signaling in the brain via the synthesis of acetylcholine. Via its metabolites, it participates in pathways that regulate methylation of genes related to memory and cognitive functions at different stages of development. Choline-related functions have been dysregulated in some neurodegenerative diseases suggesting choline role in influencing mental health across the lifespan.
MeSH term(s)	Animals ; Brain/drug effects ; Brain/growth & development ; Choline/administration & dosage ; Choline/metabolism ; Cognition/drug effects ; DNA Methylation/drug effects ; Diet ; Dietary Supplements ; Epigenesis, Genetic ; Epigenomics ; Female ; Humans ; Maternal Nutritional Physiological Phenomena ; Memory/drug effects ; Micronutrients/administration & dosage ; Micronutrients/metabolism ; Neurodegenerative Diseases/pathology ; Neurodegenerative Diseases/prevention & control ; Neuroprotective Agents/administration & dosage ; Neuroprotective Agents/metabolism
Chemical Substances	Micronutrients ; Neuroprotective Agents ; Choline (N91BDP6H0X)
Language	English
Publishing date	2019-12-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu11122995
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Choline, the brain and neurodegeneration: insights from epigenetics.

Bekdash, Rola A

Frontiers in bioscience (Landmark edition)

2018 Volume 23, Issue 6, Page(s) 1113–1143

Abstract: Neurodegenerative disorders are a major public health problem worldwide with huge socioeconomic effect. Recent evidence suggests that neurodegeneration is not only caused by genetic factors but also affected by environmental factors including nutrients. ... ...

Abstract	Neurodegenerative disorders are a major public health problem worldwide with huge socioeconomic effect. Recent evidence suggests that neurodegeneration is not only caused by genetic factors but also affected by environmental factors including nutrients. Environmental influences have been shown to cause epigenetic modifications in the brain with long-lasting effects on behavior if they occur in early life. It has been suggested that early nutritional intervention that includes choline, betaine, VitB6, VitB12 and/or folic acid could attenuate decline in cognitive functions. Recently, choline emerged as an essential micronutrient for normal brain development and an epigenetic modifier of the genome that could alter neuronal gene methylation, expression and activity. Choline maintains the structural and functional integrity of membranes and regulates cholinergic neurotransmission via the synthesis of acetylcholine. Choline-related functions have been shown to be dysregulated in several neurodegenerative disorders suggesting a potential role of nutrients in mental health. We will discuss the role of epigenetic mechanisms in neurodegeneration and how nutrients could interact with the epigenome to protect or boost cognitive processes across the lifespan.
MeSH term(s)	Animals ; Brain/metabolism ; Choline/metabolism ; DNA Methylation ; Epigenesis, Genetic ; Histones/metabolism ; Humans ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/metabolism ; RNA, Untranslated/genetics
Chemical Substances	Histones ; RNA, Untranslated ; Choline (N91BDP6H0X)
Language	English
Publishing date	2018-01-01
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2704569-9
ISSN	2768-6698 ; 1093-9946
ISSN (online)	2768-6698
ISSN	1093-9946
DOI	10.2741/4636
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Article: Choline and the Brain: An Epigenetic Perspective.

Bekdash, Rola Aldana

Advances in neurobiology

2016 Volume 12, Page(s) 381–399

Abstract: Choline is an essential nutrient that is required for normal development of the brain. Via its metabolite betaine, it participates in the synthesis of S-adenosylmethionine, a major methyl donor for histone and DNA methylation, two epigenetic mechanisms ... ...

Abstract	Choline is an essential nutrient that is required for normal development of the brain. Via its metabolite betaine, it participates in the synthesis of S-adenosylmethionine, a major methyl donor for histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and may alter brain function. Besides its role in methyl group metabolism, choline also has pivotal functions, including the maintenance of structural integrity of membranes and modulation of cholinergic neurotransmission, functions that are often dysregulated in some neurodegenerative disorders. Emerging evidence suggests that environmental factors, including lifestyle or diet, sometimes cause epigenetic changes in the expression of neuronal genes resulting in long-term changes in brain function. Recently, choline has been implicated as an epigenetic modifier of the genome that may alter gene methylation, expression, and cellular function. Abnormal level of choline during fetal or early postnatal life has been shown to alter memory functions during adulthood. It may also contribute to the etiology of stress-related disorders and age-related decline in memory later in life. Conversely, rodent studies suggested that perinatal choline supplementation enhances performance in memory-related tasks during adulthood. In this chapter, we will focus on the impact of choline-gene interaction on brain function in early life and during adulthood. In particular, we will emphasize the potential role of choline as a neuroprotectant that may mitigate some of the adverse effects of neurodegenerative disorders and protect mental health across the lifespan.
MeSH term(s)	Animals ; Betaine/metabolism ; Brain/physiology ; Brain/physiopathology ; Choline/metabolism ; DNA Methylation ; Dietary Supplements ; Environment ; Epigenesis, Genetic ; Female ; Humans ; Pregnancy
Chemical Substances	Betaine (3SCV180C9W) ; Choline (N91BDP6H0X)
Language	English
Publishing date	2016-09-17
Publishing country	United States
Document type	Journal Article
ISSN	2190-5215
ISSN	2190-5215
DOI	10.1007/978-3-319-28383-8_21
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