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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 76195

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Dr. M. Hasan Mohajeri

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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
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Special Issue Information

Dear Colleagues,

The focus of this Special Issue is “Nutrition and the Central Nervous System”. The brain is, as a very specialized and one of the most metabolically active organs of the body, dependent on a steady and sufficient supply of dietary ingredients. The critical role of the diet for brain development as well as for proper CNS functioning and the possible preventative roles against neurodegenerative and neurological conditions is commonly accepted. The overarching aim of this SI is pinpointing the mechanisms of action and publishing state-of-the art contributions discussing the roles that nutritional compounds play in the development, maintenance and aging of the CNS.

The mode of action of a given ingredient, the specific effect of a certain diet on a CNS function or disease, as well as epidemiological evaluations demonstrating the consequences of a change in the microbiome affecting brain function 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:

Central nervous system
Neurogenesis
Brain development
Brain aging
Microbiome and brain
Age-related brain dysfunction
Dietary bioactives
Malnutrition
Nutrition and chronic conditions
Genetic predisposition

PD Dr. M. Hasan Mohajeri
Guest Editor

Manuscript Submission Information

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

Central nervous system
Neurogenesis
Brain development
Brain aging
Microbiome and brain
Age-related brain dysfunction
Dietary bioactives
Malnutrition
Nutrition and chronic conditions
Genetic predisposition

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Published Papers (10 papers)

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Research

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16 pages, 615 KiB

Open AccessArticle

Dietary Fructose Intake and Hippocampal Structure and Connectivity during Childhood

by Kristi A. Clark, Jasmin M. Alves, Sabrina Jones, Alexandra G. Yunker, Shan Luo, Ryan P. Cabeen, Brendan Angelo, Anny H. Xiang and Kathleen A. Page

Nutrients 2020, 12(4), 909; https://doi.org/10.3390/nu12040909 - 26 Mar 2020

Cited by 10 | Viewed by 4435

Abstract

In rodent literature, there is evidence that excessive fructose consumption during development has a detrimental impact on hippocampal structure and function. In this study of 103 children ages 7–11 years old, we investigated whether dietary fructose intake was related to alterations in hippocampal volume and connectivity in humans. To examine if these associations were specific to fructose or were related to dietary sugars intake in general, we explored relationships between dietary intake of added sugars and the monosaccharide, glucose, on the same brain measures. We found that increased dietary intake of fructose, measured as a percentage of total calories, was associated with both an increase in the volume of the CA2/3 subfield of the right hippocampus and increased axial, radial, and mean diffusivity in the prefrontal connections of the right cingulum. These findings are consistent with the idea that increased fructose consumption during childhood may be associated with an inflammatory process, and/or decreases or delays in myelination and/or pruning. Increased habitual consumption of glucose or added sugar in general were associated with an increased volume of right CA2/3, but not with any changes in the connectivity of the hippocampus. These findings support animal data suggesting that higher dietary intake of added sugars, particularly fructose, are associated with alterations in hippocampal structure and connectivity during childhood. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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12 pages, 1864 KiB

Open AccessArticle

Evaluating the Memory Enhancing Effects of Angelica gigas in Mouse Models of Mild Cognitive Impairments

by Minsang Kim, Minah Song, Hee-Jin Oh, Jin Hui, Woori Bae, Jihwan Shin, Sang-Dock Ji, Young Ho Koh, Joo Won Suh, Hyunwoo Park and Sungho Maeng

Nutrients 2020, 12(1), 97; https://doi.org/10.3390/nu12010097 - 30 Dec 2019

Cited by 11 | Viewed by 3796

Abstract

(1) Background: By 2050, it is estimated that 130 million people will be diagnosed with dementia, and currently approved medicines only slow the progression. So preventive intervention is important to treat dementia. Mild cognitive impairment is a condition characterized by some deterioration in cognitive function and increased risk of progressing to dementia. Therefore, the treatment of mild cognitive impairment (MCI) is a possible way to prevent dementia. Angelica gigas reduces neuroinflammation, improves circulation, and inhibits cholinesterase, which can be effective in the prevention of Alzheimer’s disease and vascular dementia and the progression of mild cognitive impairment. (2) Methods: Angelica gigas (AG) extract 1 mg/kg was administered to mildly cognitive impaired mice, models based on mild traumatic brain injury and chronic mild stress. Then, spatial, working, and object recognition and fear memory were measured. (3) Result: Angelica gigas improved spatial learning, working memory, and suppressed fear memory in the mild traumatic brain injury model. It also improved spatial learning and suppressed cued fear memory in the chronic mild stress model animals. (4) Conclusions: Angelica gigas can improve cognitive symptoms in mild cognitive impairment model mice. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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12 pages, 1974 KiB

Open AccessArticle

Equol Pretreatment Protection of SH-SY5Y Cells against Aβ (25–35)-Induced Cytotoxicity and Cell-Cycle Reentry via Sustaining Estrogen Receptor Alpha Expression

by Meng-Chao Tsai, Shyh-Hsiang Lin, Kiswatul Hidayah and Ching-I Lin

Nutrients 2019, 11(10), 2356; https://doi.org/10.3390/nu11102356 - 3 Oct 2019

Cited by 23 | Viewed by 4128

Abstract

β-amyloid formation in the brain is one of the characteristics of Alzheimer’s disease. Exposure to this peptide may result in reentry into the cell cycle leading to cell death. The phytoestrogen equol has similar biological effects as estrogen without the side effects. This study investigated the possible mechanism of the neuron cell-protecting effect of equol during treatment with Aβ. SH-SY5Y neuroblastoma cells were treated with either 1 μM S-equol or 10 nM 17β-estradiol for 24 h prior to 1 μM Aβ (25–35) exposure. After 24 h exposure to Aβ (25–35), a significant reduction in cell survival and a reentry into the cell cycle process accompanied by increased levels of cyclin D1 were observed. The expressions of estrogen receptor alpha (ERα) and its coactivator, steroid receptor coactivator-1 (SRC-1), were also significantly downregulated by Aβ (25–35) in parallel with activated extracellular signal-regulated kinase (ERK)1/2. However, pretreatment of cells with S-equol or 17β-estradiol reversed these effects. Treatment with the ER antagonist, ICI-182,780 (1 μM), completely blocked the effects of S-equol and 17β-estradiol on cell viability, ERα, and ERK1/2 after Aβ (25–35) exposure. These data suggest that S-equol possesses a neuroprotective potential as it effectively antagonizes Aβ (25–35)-induced cell cytotoxicity and prevents cell cycle reentry in SH-SY5Y cells. The mechanism underlying S-equol neuroprotection might involve ERα-mediated pathways. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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18 pages, 1754 KiB

Open AccessArticle

Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD

by Wei Wang, Daisuke Tanokashira, Yusuke Fukui, Megumi Maruyama, Chiemi Kuroiwa, Takashi Saito, Takaomi C. Saido and Akiko Taguchi

Nutrients 2019, 11(8), 1942; https://doi.org/10.3390/nu11081942 - 17 Aug 2019

Cited by 14 | Viewed by 6611

Abstract

The biological effects of insulin signaling are regulated by the phosphorylation of insulin receptor substrate 1 (IRS1) at serine (Ser) residues. In the brain, phosphorylation of IRS1 at specific Ser sites increases in patients with Alzheimer’s disease (AD) and its animal models. However, whether the activation of Ser sites on neural IRS1 is related to any type of memory decline remains unclear. Here, we show the modifications of IRS1 through its phosphorylation at etiology-specific Ser sites in various animal models of memory decline, such as diabetic, aged, and amyloid precursor protein (APP) knock-in ^NL-G-F (APPKI^NL-G-F) mice. Substantial phosphorylation of IRS1 at specific Ser sites occurs in type 2 diabetes- or age-related memory deficits independently of amyloid-β (Aβ). Furthermore, we present the first evidence that, in APPKI^NL-G-F mice showing Aβ42 elevation, the increased phosphorylation of IRS1 at multiple Ser sites occurs without memory impairment. Our findings suggest that the phosphorylation of IRS1 at specific Ser sites is a potential marker of Aβ-unrelated memory deficits caused by type 2 diabetes and aging; however, in Aβ-related memory decline, the modifications of IRS1 may be a marker of early detection of Aβ42 elevation prior to the onset of memory decline in AD. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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18 pages, 8170 KiB

Open AccessArticle

Natural Dietary Supplementation of Curcumin Protects Mice Brains against Ethanol-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment via Nrf2/TLR4/RAGE Signaling

by Muhammad Ikram, Kamran Saeed, Amjad Khan, Tahir Muhammad, Muhammad Sohail Khan, Min Gi Jo, Shafiq Ur Rehman and Myeong Ok Kim

Nutrients 2019, 11(5), 1082; https://doi.org/10.3390/nu11051082 - 15 May 2019

Cited by 84 | Viewed by 7891

Abstract

The aim of the current study was to explore the underlying neuroprotective mechanisms of curcumin (50 mg/kg, for six weeks) against ethanol (5 mg/kg i.p., for six weeks) induced oxidative stress and inflammation-mediated cognitive dysfunction in mice. According to our findings, ethanol triggered reactive oxygen species (ROS), apoptosis, neuroinflammation, and memory impairment, which were significantly inhibited with the administration of curcumin, as assessed by ROS, lipid peroxidation (LPO), and Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/Heme-oxygenase-1) expression in the experimental mice brains. Moreover, curcumin regulated the expression of the glial cell markers in ethanol-treated mice brains, as analyzed by the relative expression TLR4 (Toll like Receptor 4), RAGE (Receptor for Advanced Glycations End products), GFAP (Glial fibrillary acidic protein), and Iba-1 (Ionized calcium binding adaptor molecule 1), through Western blot and confocal microscopic analysis. Moreover, our results showed that curcumin downregulated the expression of p-JNK (Phospo c-Jun N-Terminal Kinase), p-NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), and its downstream targets, as assessed by Western blot and confocal microscopic analysis. Finally, the expression of synaptic proteins and the behavioral results also supported the hypothesis that curcumin may inhibit memory dysfunction and behavioral alterations associated with ethanol intoxication. Altogether, to the best of our knowledge, we believe that curcumin may serve as a potential, promising, and cheaply available neuroprotective compound against ethanol-associated neurodegenerative diseases. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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14 pages, 1991 KiB

Open AccessArticle

The Chinese Herbal Formula PAPZ Ameliorates Behavioral Abnormalities in Depressive Mice

by Huiling Chen, Qing Huang, Shunjia Zhang, Kaiqiang Hu, Wenxiang Xiong, Lingyun Xiao, Renhuai Cong, Qingfei Liu and Zhao Wang

Nutrients 2019, 11(4), 859; https://doi.org/10.3390/nu11040859 - 16 Apr 2019

Cited by 16 | Viewed by 4632

Abstract

Major depressive disorder (MDD) is a chronic mental disorder characterized by mixed symptoms and complex pathogenesis. With long history of practical application, traditional Chinese medicine (TCM) offers many herbs for the treatment and rehabilitation of chronic disease. In this study, we developed a modified Chinese herbal formula using Panax ginseng, Angelica Sinensis, Polygala tenuifolia Willd, and Ziziphi spinosae Semen (PAPZ), based on an ancient TCM prescription. The antidepressant effects of PAPZ were investigated with a corticosterone (CORT) model of depression in mice. Our results showed that administration of PAPZ ameliorated depression-like phenotypes in the CORT model. An anatomic study showed that chronic PAPZ administration upregulated the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissue. The enzyme activity of superoxide dismutase was enhanced in hippocampal tissue, in line with a decreased malondialdehyde level. Taken together, these findings suggested that PAPZ has therapeutic effects in a mice depression model through increasing protein expression of BDNF and improving the anti-oxidation ability of the brain. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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19 pages, 1397 KiB

Open AccessArticle

Palatability of Goat’s versus Cow’s Milk: Insights from the Analysis of Eating Behavior and Gene Expression in the Appetite-Relevant Brain Circuit in Laboratory Animal Models

by Anica Klockars, Erin L. Wood, Sarah N. Gartner, Laura K. McColl, Allen S. Levine, Elizabeth A. Carpenter, Colin G. Prosser and Pawel K. Olszewski

Nutrients 2019, 11(4), 720; https://doi.org/10.3390/nu11040720 - 28 Mar 2019

Cited by 7 | Viewed by 4113

Abstract

Goat’s (GM) and cow’s milk (CM) are dietary alternatives with select health benefits shown in human and animal studies. Surprisingly, no systematic analysis of palatability or preference for GM vs. CM has been performed to date. Here, we present a comprehensive investigation of short-term intake and palatability profiles of GM and CM in laboratory mice and rats. We studied consumption in no-choice and choice scenarios, including meal microstructure, and by using isocaloric milks and milk-enriched solid diets. Feeding results are accompanied by qPCR data of relevant genes in the energy balance-related hypothalamus and brain stem, and in the nucleus accumbens, which regulates eating for palatability. We found that GM and CM are palatable to juvenile, adult, and aged rodents. Given a choice, animals prefer GM- to CM-based diets. Analysis of meal microstructure using licking patterns points to enhanced palatability of and, possibly, greater motivation toward GM over CM. Most profound changes in gene expression after GM vs. CM were associated with the brain systems driving consumption for reward. We conclude that, while both GM and CM are palatable, GM is preferred over CM by laboratory animals, and this preference is driven by central mechanisms controlling eating for pleasure. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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11 pages, 1335 KiB

Open AccessArticle

Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System

by Yasuhisa Ano, Tatsuhiro Ayabe, Rena Ohya, Keiji Kondo, Shiho Kitaoka and Tomoyuki Furuyashiki

Nutrients 2019, 11(2), 348; https://doi.org/10.3390/nu11020348 - 6 Feb 2019

Cited by 28 | Viewed by 5828

Abstract

Tryptophan-tyrosine (WY)-related peptides including the β-lactopeptide of the glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improve spatial memory. However, whether and how the WY dipeptide as the core sequence in WY-related peptides improves memory functions has not been investigated. This study assessed the pharmacological effects of the WY dipeptide on memory impairment to elucidate the mechanisms. Here, we showed that oral administration of dipeptides of WY, tryptophan-methionine (WM), tryptophan-valine, tryptophan-leucine, and tryptophan-phenylalanine improved spontaneous alternation of the Y-maze test in scopolamine-induced amnesic mice. In contrast, tyrosine-tryptophan, methionine-tryptophan, tryptophan, tyrosine, and methionine had no effect. These results indicated that the conformation of dipeptides with N-terminal tryptophan is required for their memory improving effects. WY dipeptide inhibited the monoamine oxidase B activity in vitro and increased dopamine levels in the hippocampus and frontal cortex, whereas tryptophan did not cause these effects. In addition, the treatment with SCH-23390, a dopamine D1-like receptor antagonist, and the knockdown of the hippocampal dopamine D1 receptor partially attenuated the memory improvement induced by the WY dipeptide. Importantly, WY dipeptide improved the spontaneous alternations of the Y-maze test in aged mice. These results suggest that the WY dipeptide restores memory impairments by augmenting dopaminergic activity. The development of supplements rich in these peptides might help to prevent age-related cognitive decline. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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25 pages, 735 KiB

Open AccessReview

The Potential Influence of the Bacterial Microbiome on the Development and Progression of ADHD

by Stephanie Bull-Larsen and M. Hasan Mohajeri

Nutrients 2019, 11(11), 2805; https://doi.org/10.3390/nu11112805 - 17 Nov 2019

Cited by 66 | Viewed by 13729

Abstract

The latest research cumulates staggering information about the correlation between the microbiota-gut-brain axis and neurodevelopmental disorders. This review aims to shed light on the potential influence of the microbiome on the development of the most prevalent neurodevelopmental disease, attention-deficit-hyperactive disorder (ADHD). As the etiology and pathophysiology of ADHD are still unclear, finding viable biomarkers and effective treatment still represent a challenge. Therefore, we focused on factors that have been associated with a higher risk of developing ADHD, while simultaneously influencing the microbial composition. We reviewed the effect of a differing microbial makeup on neurotransmitter concentrations important in the pathophysiology of ADHD. Additionally, we deduced factors that correlate with a high prevalence of ADHD, while simultaneously affecting the gut microbiome, such as emergency c-sections, and premature birth as the former leads to a decrease of the gut microbial diversity and the latter causes neuroprotective Lactobacillus levels to be reduced. Also, we assessed nutritional influences, such as breastfeeding, ingestion of short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs) on the host′s microbiome and development of ADHD. Finally, we discussed the potential significance of Bifidobacterium as a biomarker for ADHD, the importance of preventing premature birth as prophylaxis and nutrition as a prospective therapeutic measurement against ADHD. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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22 pages, 3208 KiB

Open AccessReview

From Probiotics to Psychobiotics: Live Beneficial Bacteria Which Act on the Brain-Gut Axis

by Luis G. Bermúdez-Humarán, Eva Salinas, Genaro G. Ortiz, Luis J. Ramirez-Jirano, J. Alejandro Morales and Oscar K. Bitzer-Quintero

Nutrients 2019, 11(4), 890; https://doi.org/10.3390/nu11040890 - 20 Apr 2019

Cited by 115 | Viewed by 19774

Abstract

There is an important relationship between probiotics, psychobiotics and cognitive and behavioral processes, which include neurological, metabolic, hormonal and immunological signaling pathways; the alteration in these systems may cause alterations in behavior (mood) and cognitive level (learning and memory). Psychobiotics have been considered key elements in affective disorders and the immune system, in addition to their effect encompassing the regulation of neuroimmune regulation and control axes (the hypothalamic-pituitary-adrenal axis or HPA, the sympathetic-adrenal-medullary axis or SAM and the inflammatory reflex) in diseases of the nervous system. The aim of this review is to summarize the recent findings about psychobiotics, the brain-gut axis and the immune system. The review focuses on a very new and interesting field that relates the microbiota of the intestine with diseases of the nervous system and its possible treatment, in neuroimmunomodulation area. Indeed, although probiotic bacteria will be concentrated after ingestion, mainly in the intestinal epithelium (where they provide the host with essential nutrients and modulation of the immune system), they may also produce neuroactive substances which act on the brain-gut axis. Full article

(This article belongs to the Special Issue Nutrition and Central Nervous System)

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