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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutritional Epidemiology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 66445

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Special Issue Editor

Dr. M. Hasan Mohajeri

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Guest Editor

Department of Medicine, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
Interests: aging; Alzheimer’s disease; neurodegeneration; ADHD; nutrition; gut–brain axis; drug development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue focuses on factors that are implicated in the development of the brain, and thus have the potential to influence its functions. On the one hand, the brain depends on a steady and sufficient supply of oxygen and dietary ingredients for proper functioning. On the other hand, genetic predispositions and epigenetic and environmental factors may influence brain development and function. Imbalance in any of these factors may lead to the manifestation of developmental disorders of young ages, compromised daily capabilities, or age-associated brain disorders.

The goal of this Special Issue is to publish state-of-the-art contributions discussing the role of nutritional compounds, genetic factors, etc., on brain development, its functions, and aging. Mechanistic as well as epidemiological studies in vitro, in vivo, and in human subjects will be considered for publication. We encourage the submission of original research articles, reviews, and meta-analyses. Potential topics may include, but are not limited to the keywords given below.

PD Dr. M. Hasan Mohajeri
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Nervous system
Neurogenesis
Brain development
Brain aging
Microbiome and brain
Genetic modifications, polymorphisms
Age-related brain dysfunction
Dietary bioactives
Malnutrition
Nutrition and chronic conditions
Genetic predisposition

Published Papers (12 papers)

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Editorial

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3 pages, 176 KiB

Open AccessEditorial

Nutrition for Brain Development

by M. Hasan Mohajeri

Nutrients 2022, 14(7), 1419; https://doi.org/10.3390/nu14071419 - 29 Mar 2022

Cited by 1 | Viewed by 2225

Abstract

This Special Issue focuses on the fundamental role of nutrition in brain development [...] Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

Research

Jump to: Editorial, Review

28 pages, 7262 KiB

Open AccessArticle

Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

by Saivageethi Nuthikattu, Dragan Milenkovic, Jennifer E. Norman, John Rutledge and Amparo Villablanca

Nutrients 2021, 13(11), 3913; https://doi.org/10.3390/nu13113913 - 01 Nov 2021

Cited by 14 | Viewed by 2883

Abstract

Diet is a modifiable risk factor for cardiovascular disease (CVD) and dementia, yet relatively little is known about the effect of a high glycemic diet (HGD) on the brain’s microvasculature. The objective of our study was to determine the molecular effects of an HGD on hippocampal microvessels and cognitive function and determine if a soluble epoxide hydrolase (sEH) inhibitor (sEHI), known to be vasculoprotective and anti-inflammatory, modulates these effects. Wild type male mice were fed a low glycemic diet (LGD, 12% sucrose/weight) or an HGD (34% sucrose/weight) with/without the sEHI, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks. Brain hippocampal microvascular gene expression was assessed by microarray and data analyzed using a multi-omic approach for differential expression of protein and non-protein-coding genes, gene networks, functional pathways, and transcription factors. Global hippocampal microvascular gene expression was fundamentally different for mice fed the HGD vs. the LGD. The HGD response was characterized by differential expression of 608 genes involved in cell signaling, neurodegeneration, metabolism, and cell adhesion/inflammation/oxidation effects reversible by t-AUCB and hence sEH inhibitor correlated with protection against Alzheimer’s dementia. Ours is the first study to demonstrate that high dietary glycemia contributes to brain hippocampal microvascular inflammation through sEH. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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11 pages, 370 KiB

Open AccessArticle

Associations between the Mediterranean Diet Pattern and Weight Status and Cognitive Development in Preschool Children

by Federico Granziera, Maria Angela Guzzardi and Patricia Iozzo

Nutrients 2021, 13(11), 3723; https://doi.org/10.3390/nu13113723 - 22 Oct 2021

Cited by 18 | Viewed by 2907

Abstract

Cognitive dysfunctions are a global health concern. Early-life diet and weight status may contribute to children’s cognitive development. For this reason, we explored the associations between habitual food consumption, body mass index (BMI) and cognitive outcomes in 54 preschool children belonging to the Pisa birth Cohort (PISAC). We estimated groups of foods, nutrients and calorie intakes through a food frequency questionnaire (FFQ) and Italian national databases. Then, we adopted the Mediterranean diet (MD) score to assess relative MD adherence. Cognition was examined using the Griffiths Mental Development Scales-Extended Revised (GMDS-ER). We found that higher, compared to low and moderate, adherence to MD was associated with higher performance scores. Furthermore, white meat consumption was positively related to BMI, and BMI (age–gender specific, z-scores) categories were negatively related to practical reasoning scores. All associations were independent of maternal IQ estimates, parents’ socioeconomic status, exclusive/non-exclusive breastfeeding, actual age at cognitive assessment and gender. In conclusion, in preschool children, very high adherence to MD seemed protective, whereas BMI (reinforced by the intake of white meat) was negatively associated with cognition. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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14 pages, 9429 KiB

Open AccessArticle

Spearmint Extract Containing Rosmarinic Acid Suppresses Amyloid Fibril Formation of Proteins Associated with Dementia

by Kenjirou Ogawa, Ayumi Ishii, Aimi Shindo, Kunihiro Hongo, Tomohiro Mizobata, Tetsuya Sogon and Yasushi Kawata

Nutrients 2020, 12(11), 3480; https://doi.org/10.3390/nu12113480 - 13 Nov 2020

Cited by 11 | Viewed by 3634

Abstract

Neurological dementias such as Alzheimer’s disease and Lewy body dementia are thought to be caused in part by the formation and deposition of characteristic insoluble fibrils of polypeptides such as amyloid beta (Aβ), Tau, and/or α-synuclein (αSyn). In this context, it is critical to suppress and remove such aggregates in order to prevent and/or delay the progression of dementia in these ailments. In this report, we investigated the effects of spearmint extract (SME) and rosmarinic acid (RA; the major component of SME) on the amyloid fibril formation reactions of αSyn, Aβ, and Tau proteins in vitro. SME or RA was added to soluble samples of each protein and the formation of fibrils was monitored by thioflavin T (ThioT) binding assays and transmission electron microscopy (TEM). We also evaluated whether preformed amyloid fibrils could be dissolved by the addition of RA. Our results reveal for the first time that SME and RA both suppress amyloid fibril formation, and that RA could disassemble preformed fibrils of αSyn, Aβ, and Tau into non-toxic species. Our results suggest that SME and RA may potentially suppress amyloid fibrils implicated in the progression of Alzheimer’s disease and Lewy body dementia in vivo, as well. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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21 pages, 528 KiB

Open AccessArticle

Cognitive Outcomes and Relationships with Phenylalanine in Phenylketonuria: A Comparison between Italian and English Adult Samples

by Cristina Romani, Filippo Manti, Francesca Nardecchia, Federica Valentini, Nicoletta Fallarino, Claudia Carducci, Sabrina De Leo, Anita MacDonald, Liana Palermo and Vincenzo Leuzzi

Nutrients 2020, 12(10), 3033; https://doi.org/10.3390/nu12103033 - 03 Oct 2020

Cited by 10 | Viewed by 2927

Abstract

We aimed to assess if the same cognitive batteries can be used cross-nationally to monitor the effect of Phenylketonuria (PKU). We assessed whether a battery, previously used with English adults with PKU (AwPKU), was also sensitive to impairments in Italian AwPKU. From our original battery, we selected a number of tasks that comprehensively assessed visual attention, visuo-motor coordination, executive functions (particularly, reasoning, planning, and monitoring), sustained attention, and verbal and visual memory and learning. When verbal stimuli/or responses were involved, stimuli were closely matched between the two languages for psycholinguistic variables. We administered the tasks to 19 Italian AwPKU and 19 Italian matched controls and compared results from with 19 English AwPKU and 19 English matched controls selected from a previously tested cohort. Participant election was blind to cognitive performance and metabolic control, but participants were closely matched for age and education. The Italian AwPKU group had slightly worse metabolic control but showed levels of performance and patterns of impairment similar to the English AwPKU group. The Italian results also showed extensive correlations between adult cognitive measures and metabolic measures across the life span, both in terms of Phenylalanine (Phe) levels and Phe fluctuations, replicating previous results in English. These results suggest that batteries with the same and/or matched tasks can be used to assess cognitive outcomes across countries allowing results to be compared and accrued. Future studies should explore potential differences in metabolic control across countries to understand what variables make metabolic control easier to achieve. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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23 pages, 4281 KiB

Open AccessArticle

Maternal Protein Restriction in Rats Alters the Expression of Genes Involved in Mitochondrial Metabolism and Epitranscriptomics in Fetal Hypothalamus

by Morgane Frapin, Simon Guignard, Dimitri Meistermann, Isabelle Grit, Valentine S. Moullé, Vincent Paillé, Patricia Parnet and Valérie Amarger

Nutrients 2020, 12(5), 1464; https://doi.org/10.3390/nu12051464 - 19 May 2020

Cited by 6 | Viewed by 3595

Abstract

Fetal brain development is closely dependent on maternal nutrition and metabolic status. Maternal protein restriction (PR) is known to be associated with alterations in the structure and function of the hypothalamus, leading to impaired control of energy homeostasis and food intake. The objective of this study was to identify the cellular and molecular systems underlying these effects during fetal development. We combined a global transcriptomic analysis on the fetal hypothalamus from a rat model of maternal PR with in vitro neurosphere culture and cellular analyses. Several genes encoding proteins from the mitochondrial respiratory chain complexes were overexpressed in the PR group and mitochondrial metabolic activity in the fetal hypothalamus was altered. The level of the N6-methyladenosine epitranscriptomic mark was reduced in the PR fetuses, and the expression of several genes involved in the writing/erasing/reading of this mark was indeed altered, as well as genes encoding several RNA-binding proteins. Additionally, we observed a higher number of neuronal-committed progenitors at embryonic day 17 (E17) in the PR fetuses. Together, these data strongly suggest a metabolic adaptation to the amino acid shortage, combined with the post-transcriptional control of protein expression, which might reflect alterations in the control of the timing of neuronal progenitor differentiation. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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18 pages, 1400 KiB

Open AccessArticle

Maternal Diet Influences the Reinstatement of Cocaine-Seeking Behavior and the Expression of Melanocortin-4 Receptors in Female Offspring of Rats

by Dawid Gawliński, Kinga Gawlińska, Małgorzata Frankowska and Małgorzata Filip

Nutrients 2020, 12(5), 1462; https://doi.org/10.3390/nu12051462 - 19 May 2020

Cited by 14 | Viewed by 4704

Abstract

Recent studies have emphasized the role of the maternal diet in the development of mental disorders in offspring. Substance use disorder is a major global health and economic burden. Therefore, the search for predisposing factors for the development of this disease can contribute to reducing the health and social damage associated with addiction. In this study, we focused on the impact of the maternal diet on changes in melanocortin-4 (MC-4) receptors as well as on behavioral changes related to cocaine addiction. Rat dams consumed a high-fat diet (HFD), high-sugar diet (HSD, rich in sucrose), or mixed diet (MD) during pregnancy and lactation. Using an intravenous cocaine self-administration model, the susceptibility of female offspring to cocaine reward and cocaine-seeking propensities was evaluated. In addition, the level of MC-4 receptors in the rat brain structures related to cocaine reward and relapse was assessed. Modified maternal diets did not affect cocaine self-administration in offspring. However, the maternal HSD enhanced cocaine-seeking behavior in female offspring. In addition, we observed that the maternal HSD and MD led to increased expression of MC-4 receptors in the nucleus accumbens, while increased MC-4 receptor levels in the dorsal striatum were observed after exposure to the maternal HSD and HFD. Taken together, it can be concluded that a maternal HSD is an important factor that triggers cocaine-seeking behavior in female offspring and the expression of MC-4 receptors. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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Review

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22 pages, 590 KiB

Open AccessReview

The Role of the Gut Microbiota in the Development and Progression of Major Depressive and Bipolar Disorder

by Tom Knuesel and M. Hasan Mohajeri

Nutrients 2022, 14(1), 37; https://doi.org/10.3390/nu14010037 - 23 Dec 2021

Cited by 40 | Viewed by 7507

Abstract

A growing number of studies in rodents indicate a connection between the intestinal microbiota and the brain, but comprehensive human data is scarce. Here, we systematically reviewed human studies examining the connection between the intestinal microbiota and major depressive and bipolar disorder. In this review we discuss various changes in bacterial abundance, particularly on low taxonomic levels, in terms of a connection with the pathophysiology of major depressive and bipolar disorder, their use as a diagnostic and treatment response parameter, their health-promoting potential, as well as novel adjunctive treatment options. The diversity of the intestinal microbiota is mostly decreased in depressed subjects. A consistent elevation of phylum Actinobacteria, family Bifidobacteriaceae, and genus Bacteroides, and a reduction of family Ruminococcaceae, genus Faecalibacterium, and genus Roseburia was reported. Probiotics containing Bifidobacterium and/or Lactobacillus spp. seemed to improve depressive symptoms, and novel approaches with different probiotics and synbiotics showed promising results. Comparing twin studies, we report here that already with an elevated risk of developing depression, microbial changes towards a “depression-like” microbiota were found. Overall, these findings highlight the importance of the microbiota and the necessity for a better understanding of its changes contributing to depressive symptoms, potentially leading to new approaches to alleviate depressive symptoms via alterations of the gut microbiota. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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35 pages, 1492 KiB

Open AccessReview

Beneficial Effects of Exogenous Ketogenic Supplements on Aging Processes and Age-Related Neurodegenerative Diseases

by Zsolt Kovács, Brigitta Brunner and Csilla Ari

Nutrients 2021, 13(7), 2197; https://doi.org/10.3390/nu13072197 - 26 Jun 2021

Cited by 27 | Viewed by 12643

Abstract

Life expectancy of humans has increased continuously up to the present days, but their health status (healthspan) was not enhanced by similar extent. To decrease enormous medical, economical and psychological burden that arise from this discrepancy, improvement of healthspan is needed that leads to delaying both aging processes and development of age-related diseases, thereby extending lifespan. Thus, development of new therapeutic tools to alleviate aging processes and related diseases and to increase life expectancy is a topic of increasing interest. It is widely accepted that ketosis (increased blood ketone body levels, e.g., β-hydroxybutyrate) can generate neuroprotective effects. Ketosis-evoked neuroprotective effects may lead to improvement in health status and delay both aging and the development of related diseases through improving mitochondrial function, antioxidant and anti-inflammatory effects, histone and non-histone acetylation, β-hydroxybutyrylation of histones, modulation of neurotransmitter systems and RNA functions. Administration of exogenous ketogenic supplements was proven to be an effective method to induce and maintain a healthy state of nutritional ketosis. Consequently, exogenous ketogenic supplements, such as ketone salts and ketone esters, may mitigate aging processes, delay the onset of age-associated diseases and extend lifespan through ketosis. The aim of this review is to summarize the main hallmarks of aging processes and certain signaling pathways in association with (putative) beneficial influences of exogenous ketogenic supplements-evoked ketosis on lifespan, aging processes, the most common age-related neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis), as well as impaired learning and memory functions. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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Graphical abstract

14 pages, 640 KiB

Open AccessReview

The Potential Roles of Blood–Brain Barrier and Blood–Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

by Shannon Morgan McCabe and Ningning Zhao

Nutrients 2021, 13(6), 1833; https://doi.org/10.3390/nu13061833 - 27 May 2021

Cited by 18 | Viewed by 8511

Abstract

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a “privileged” organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood–brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood–CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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40 pages, 1685 KiB

Open AccessEditor’s ChoiceReview

The Role of Gut Bacterial Metabolites in Brain Development, Aging and Disease

by Shirley Mei-Sin Tran and M. Hasan Mohajeri

Nutrients 2021, 13(3), 732; https://doi.org/10.3390/nu13030732 - 25 Feb 2021

Cited by 89 | Viewed by 9282

Abstract

In the last decade, emerging evidence has reported correlations between the gut microbiome and human health and disease, including those affecting the brain. We performed a systematic assessment of the available literature focusing on gut bacterial metabolites and their associations with diseases of the central nervous system (CNS). The bacterial metabolites short-chain fatty acids (SCFAs) as well as non-SCFAs like amino acid metabolites (AAMs) and bacterial amyloids are described in particular. We found significantly altered SCFA levels in patients with autism spectrum disorder (ASD), affective disorders, multiple sclerosis (MS) and Parkinson’s disease (PD). Non-SCFAs yielded less significantly distinct changes in faecal levels of patients and healthy controls, with the majority of findings were derived from urinary and blood samples. Preclinical studies have implicated different bacterial metabolites with potentially beneficial as well as detrimental mechanisms in brain diseases. Examples include immunomodulation and changes in catecholamine production by histone deacetylase inhibition, anti-inflammatory effects through activity on the aryl hydrocarbon receptor and involvement in protein misfolding. Overall, our findings highlight the existence of altered bacterial metabolites in patients across various brain diseases, as well as potential neuroactive effects by which gut-derived SCFAs, p-cresol, indole derivatives and bacterial amyloids could impact disease development and progression. The findings summarized in this review could lead to further insights into the gut–brain–axis and thus into potential diagnostic, therapeutic or preventive strategies in brain diseases. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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16 pages, 1126 KiB

Open AccessReview

The Protective and Long-Lasting Effects of Human Milk Oligosaccharides on Cognition in Mammals

by Sylvia Docq, Marcia Spoelder, Wendan Wang and Judith R. Homberg

Nutrients 2020, 12(11), 3572; https://doi.org/10.3390/nu12113572 - 21 Nov 2020

Cited by 14 | Viewed by 4194

Abstract

Over the last few years, research indicated that Human Milk Oligosaccharides (HMOs) may serve to enhance cognition during development. HMOs hereby provide an exciting avenue in the understanding of the molecular mechanisms that contribute to cognitive development. Therefore, this review aims to summarize the reported observations regarding the effects of HMOs on memory and cognition in rats, mice and piglets. Our main findings illustrate that the administration of fucosylated (single or combined with Lacto-N-neoTetraose (LNnT) and other oligosaccharides) and sialylated HMOs results in marked improvements in spatial memory and an accelerated learning rate in operant tasks. Such beneficial effects of HMOs on cognition already become apparent during infancy, especially when the behavioural tasks are cognitively more demanding. When animals age, its effects become increasingly more apparent in simpler tasks as well. Furthermore, the combination of HMOs with other oligosaccharides yields different effects on memory performance as opposed to single HMO administration. In addition, an enhanced hippocampal long-term potentiation (LTP) response both at a young and at a mature age are reported as well. These results point towards the possibility that HMOs administered either in singular or combination forms have long-lasting, beneficial effects on memory and cognition in mammals. Full article

(This article belongs to the Special Issue Nutrition for Brain Development)

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