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12 pages, 3976 KiB

Open AccessArticle

Maternal Dietary Deficiencies in Folic Acid and Choline Result in Larger Damage Volume, Reduced Neuro-Degeneration and -Inflammation and Changes in Choline Metabolites after Ischemic Stroke in Middle-Aged Offspring

by Lauren Hurley, Jesse Jauhal, Sharadyn Ille, Kasey Pull, Olga V. Malysheva and Nafisa M. Jadavji

Nutrients 2023, 15(7), 1556; https://doi.org/10.3390/nu15071556 - 23 Mar 2023

Cited by 7 | Viewed by 1915

Abstract

Maternal dietary levels of one-carbon (1C) metabolites (folic acid and choline) during pregnancy play a vital role in neurodevelopment. However, the impact of maternal dietary deficiencies on offspring stroke outcomes later in life remains undefined. The aim of this study was to investigate [...] Read more.

Maternal dietary levels of one-carbon (1C) metabolites (folic acid and choline) during pregnancy play a vital role in neurodevelopment. However, the impact of maternal dietary deficiencies on offspring stroke outcomes later in life remains undefined. The aim of this study was to investigate the role of maternal dietary deficiencies in folic acid and choline on ischemic stroke outcomes in middle-aged offspring. Female mice were maintained on either a control or deficient diet prior to and during pregnancy and lactation. At 10 months of age ischemic stroke was induced in male and female offspring. Stroke outcome was assessed by measuring motor function and brain tissue. There was no difference in offspring motor function; however, sex differences were present. In brain tissue, maternal dietary deficiency increased ischemic damage volume and offspring from deficient mothers had reduced neurodegeneration and neuroinflammation within the ischemic region. Furthermore, there were changes in plasma 1C metabolites as a result of maternal diet and sex. Our data indicate that maternal dietary deficiencies do not impact offspring behavior after ischemic stroke but do play a role in brain histology and one-carbon metabolite levels in plasma. Additionally, this study demonstrates that the sex of mice plays an important role in stroke outcomes. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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22 pages, 3484 KiB

Open AccessArticle

Aspartame and Its Metabolites Cause Oxidative Stress and Mitochondrial and Lipid Alterations in SH-SY5Y Cells

by Lea Victoria Griebsch, Elena Leoni Theiss, Daniel Janitschke, Vincent Konrad Johannes Erhardt, Tobias Erhardt, Elodie Christiane Haas, Konstantin Nicolas Kuppler, Juliane Radermacher, Oliver Walzer, Anna Andrea Lauer, Veronika Matschke, Tobias Hartmann, Marcus Otto Walter Grimm and Heike Sabine Grimm

Nutrients 2023, 15(6), 1467; https://doi.org/10.3390/nu15061467 - 18 Mar 2023

Cited by 6 | Viewed by 7823

Abstract

Due to a worldwide increase in obesity and metabolic disorders such as type 2 diabetes, synthetic sweeteners such as aspartame are frequently used to substitute sugar in the diet. Possible uncertainties regarding aspartame’s ability to induce oxidative stress, amongst others, has led to [...] Read more.

Due to a worldwide increase in obesity and metabolic disorders such as type 2 diabetes, synthetic sweeteners such as aspartame are frequently used to substitute sugar in the diet. Possible uncertainties regarding aspartame’s ability to induce oxidative stress, amongst others, has led to the recommendation of a daily maximum dose of 40 to 50 mg per kg. To date, little is known about the effects of this non-nutritive sweetener on cellular lipid homeostasis, which, besides elevated oxidative stress, plays an important role in the pathogenesis of various diseases, including neurodegenerative diseases such as Alzheimer’s disease. In the present study, treatment of the human neuroblastoma cell line SH-SY5Y with aspartame (271.7 µM) or its three metabolites (aspartic acid, phenylalanine, and methanol (271.7 µM)), generated after digestion of aspartame in the human intestinal tract, resulted in significantly elevated oxidative stress associated with mitochondrial damage, which was illustrated with reduced cardiolipin levels, increased gene expression of SOD1/2, PINK1, and FIS1, and an increase in APF fluorescence. In addition, treatment of SH-SY5Y cells with aspartame or aspartame metabolites led to a significant increase in triacylglycerides and phospholipids, especially phosphatidylcholines and phosphatidylethanolamines, accompanied by an accumulation of lipid droplets inside neuronal cells. Due to these lipid-mediating properties, the use of aspartame as a sugar substitute should be reconsidered and the effects of aspartame on the brain metabolism should be addressed in vivo. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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12 pages, 768 KiB

Open AccessArticle

The Association of the Hypothalamic-Pituitary-Adrenal Axis with Appetite Regulation in Children with Fetal Alcohol Spectrum Disorders (FASDs)

by Rafał Podgórski, Sabina Galiniak, Artur Mazur and Agnieszka Domin

Nutrients 2023, 15(6), 1366; https://doi.org/10.3390/nu15061366 - 11 Mar 2023

Cited by 4 | Viewed by 2533

Abstract

Prenatal alcohol exposure causes growth impairment and a wide range of developmental, physical, and cognitive disorders in children, collectively referred to as fetal alcohol spectrum disorders (FASDs). In the course of FASDs, abnormalities can also affect eating behavior and nutritional status, but these [...] Read more.

Prenatal alcohol exposure causes growth impairment and a wide range of developmental, physical, and cognitive disorders in children, collectively referred to as fetal alcohol spectrum disorders (FASDs). In the course of FASDs, abnormalities can also affect eating behavior and nutritional status, but these problems have received little attention. Therefore, the aim of our study was to determine the levels of hormones involved in the action of the hypothalamic–pituitary–adrenal axis: proopiomelanocortin (POMC), cortisol, and adrenocorticotropic hormone (ACTH), in the serum of patients with FASDs. To our knowledge, none of these hormones studied have yet been evaluated in FASDs to date. We investigated 62 FASD patients and 23 healthy controls by applying an enzyme-linked immunosorbent method (ELISA). Fasting POMC levels were significantly lower in patients with FASDs (10.97 vs. 18,57 ng/mL, p = 0.039) compared to controls. However, there were no differences in cortisol concentrations. Additionally, the sex and subgroup status (fetal alcohol syndrome (FAS), neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE), and FASD risk) did not affect hormone levels. POMC was positively correlated with some clinical parameters such as age, BMI percentile, carbohydrate biomarkers, and ACTH. A positive correlation was observed between ACTH and cortisol levels, as well as ACTH and cholesterol levels. Data analysis showed no HPA axis abnormalities in the form of elevated serum cortisol and ACTH levels. Differences in POMC concentration may indicate the involvement and/or impairment of central nervous system structures in hormonal alterations in FASD individuals, caused by prenatal alcohol exposure. Hormonal dysregulation in FASDs can contribute to reduced growth and development, as well as many other disturbed processes, including neurological/neurodevelopmental dysfunctions. Further insightful studies involving a larger group of patients are needed to determine the potential impact of the measured hormones. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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14 pages, 1518 KiB

Open AccessArticle

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs

by Miriam Ouadih-Moran, Antonio Muñoz-Hoyos, Luis D’Marco, Antonio Molina-Carballo, Isabel Seiquer and Ana Checa-Ros

Nutrients 2023, 15(3), 712; https://doi.org/10.3390/nu15030712 - 31 Jan 2023

Cited by 4 | Viewed by 3435

Abstract

Background: Increasing evidence supports a neuroinflammatory basis in ADHD damaging glial function and thereby altering dopaminergic (DA) neurotransmission. Previous studies focusing on the S100B protein as a marker of glial function have shown contradictory results. We conducted a clinical trial to investigate differences [...] Read more.

Background: Increasing evidence supports a neuroinflammatory basis in ADHD damaging glial function and thereby altering dopaminergic (DA) neurotransmission. Previous studies focusing on the S100B protein as a marker of glial function have shown contradictory results. We conducted a clinical trial to investigate differences in S100B levels between ADHD patients and controls, as well as observe gradual changes in S100B concentrations after a triple therapy (TT) containing methylphenidate (MPH), melatonin (aMT) and omega-3 fatty acids (ω-3 PUFAs). Methods: 62 medication-naïve children with ADHD (ADHD-G) and 65 healthy controls (C-G) were recruited. Serum S100B was measured at baseline (T0) in ADHD-G/C-G, and three (T3) and six months (T6) after starting TT in the ADHD-G, together with attention scores. Results: A significant increase in S100B was observed in the ADHD-G vs. C-G. In the ADHD-G, significantly higher S100B values were observed for comparisons between T0–T3 and between T0–T6, accompanied by a significant improvement in attention scores for the same timepoint comparisons. No significant differences were found for S100B between T3–T6. Conclusion: Our results agree with the hypothesis of glial damage in ADHD. Further studies on the link between DA and S100B are required to explain the transient increase in S100B following TT. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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19 pages, 2202 KiB

Open AccessArticle

Fructose Diet-Associated Molecular Alterations in Hypothalamus of Adolescent Rats: A Proteomic Approach

by Chiara D’Ambrosio, Luisa Cigliano, Arianna Mazzoli, Monica Matuozzo, Martina Nazzaro, Andrea Scaloni, Susanna Iossa and Maria Stefania Spagnuolo

Nutrients 2023, 15(2), 475; https://doi.org/10.3390/nu15020475 - 16 Jan 2023

Cited by 3 | Viewed by 2656

Abstract

Background: The enhanced consumption of fructose as added sugar represents a major health concern. Due to the complexity and multiplicity of hypothalamic functions, we aim to point out early molecular alterations triggered by a sugar-rich diet throughout adolescence, and to verify their persistence [...] Read more.

Background: The enhanced consumption of fructose as added sugar represents a major health concern. Due to the complexity and multiplicity of hypothalamic functions, we aim to point out early molecular alterations triggered by a sugar-rich diet throughout adolescence, and to verify their persistence until the young adulthood phase. Methods: Thirty days old rats received a high-fructose or control diet for 3 weeks. At the end of the experimental period, treated animals were switched to the control diet for further 3 weeks, and then analyzed in comparison with those that were fed the control diet for the entire experimental period. Results: Quantitative proteomics identified 19 differentially represented proteins, between control and fructose-fed groups, belonging to intermediate filament cytoskeleton, neurofilament, pore complex and mitochondrial respiratory chain complexes. Western blotting analysis confirmed proteomic data, evidencing a decreased abundance of mitochondrial respiratory complexes and voltage-dependent anion channel 1, the coregulator of mitochondrial biogenesis PGC-1α, and the protein subunit of neurofilaments α-internexin in fructose-fed rats. Diet-associated hypothalamic inflammation was also detected. Finally, the amount of brain-derived neurotrophic factor and its high-affinity receptor TrkB, as well as of synaptophysin, synaptotagmin, and post-synaptic protein PSD-95 was reduced in sugar-fed rats. Notably, deregulated levels of all proteins were fully rescued after switching to the control diet. Conclusions: A short-term fructose-rich diet in adolescent rats induces hypothalamic inflammation and highly affects mitochondrial and cytoskeletal compartments, as well as the level of specific markers of brain function; above-reported effects are reverted after switching animals to the control diet. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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22 pages, 6403 KiB

Open AccessArticle

Lipidized PrRP Analog Exhibits Strong Anti-Obesity and Antidiabetic Properties in Old WKY Rats with Obesity and Glucose Intolerance

by Lucia Mráziková, Silvie Hojná, Petra Vaculová, Štěpán Strnad, Vladimír Vrkoslav, Helena Pelantová, Marek Kuzma, Blanka Železná, Jaroslav Kuneš and Lenka Maletínská

Nutrients 2023, 15(2), 280; https://doi.org/10.3390/nu15020280 - 5 Jan 2023

Cited by 4 | Viewed by 3352

Abstract

Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide that has potential for the treatment of obesity and its complications. Recently, we designed a palmitoylated PrRP31 analog (palm¹¹-PrRP31) that is more stable than the natural peptide and able to act centrally after peripheral [...] Read more.

Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide that has potential for the treatment of obesity and its complications. Recently, we designed a palmitoylated PrRP31 analog (palm¹¹-PrRP31) that is more stable than the natural peptide and able to act centrally after peripheral administration. This analog acted as an anti-obesity and glucose-lowering agent, attenuating lipogenesis in rats and mice with high-fat (HF) diet-induced obesity. In Wistar Kyoto (WKY) rats fed a HF diet for 52 weeks, we explored glucose intolerance, but also prediabetes, liver steatosis and insulin resistance-related changes, as well as neuroinflammation in the brain. A potential beneficial effect of 6 weeks of treatment with palm¹¹-PrRP31 and liraglutide as comparator was investigated. Liver lipid profiles, as well as urinary and plasma metabolomic profiles, were measured by lipidomics and metabolomics, respectively. Old obese WKY rats showed robust glucose intolerance that was attenuated by palm¹¹-PrRP31, but not by liraglutide treatment. On the contrary, liraglutide had a beneficial effect on insulin resistance parameters. Despite obesity and prediabetes, WKY rats did not develop steatosis owing to HF diet feeding, even though liver lipogenesis was enhanced. Plasma triglycerides and cholesterol were not increased by HFD feeding, which points to unincreased lipid transport from the liver. The liver lipid profile was significantly altered by a HF diet that remained unaffected by palm¹¹-PrRP31 or liraglutide treatment. The HF-diet-fed WKY rats revealed astrogliosis in the brain cortex and hippocampus, which was attenuated by treatment. In conclusion, this study suggested multiple beneficial anti-obesity-related effects of palm¹¹-PrRP31 and liraglutide in both the periphery and brain. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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14 pages, 4754 KiB

Open AccessArticle

Long-Term High-Fat Diet Consumption Induces Cognitive Decline Accompanied by Tau Hyper-Phosphorylation and Microglial Activation in Aging

by Zheng Liang, Xiaokang Gong, Runjia Ye, Yang Zhao, Jin Yu, Yanna Zhao and Jian Bao

Nutrients 2023, 15(1), 250; https://doi.org/10.3390/nu15010250 - 3 Jan 2023

Cited by 9 | Viewed by 4088

Abstract

High-fat diet (HFD) intake is commonly related to a substantial risk of cognitive impairment for senior citizens over 65 years of age, which constitutes a profound global health burden with several economic and social consequences. It is critical to investigate the effects of [...] Read more.

High-fat diet (HFD) intake is commonly related to a substantial risk of cognitive impairment for senior citizens over 65 years of age, which constitutes a profound global health burden with several economic and social consequences. It is critical to investigate the effects of long-term HFD consumption on cognitive function and to inspect the potential underlying mechanisms. In the present study, 9-month-old male C57BL/6 mice were randomly assigned to either a normal diet (ND, 10 kcal% fat) or an HFD diet (60 kcal% fat) for 10 months. Then a series of behavioral tests, and histological and biochemistry examinations of the hippocampus and cortex proceeded. We found that long-term HFD-fed aged mice exhibited cognitive function decline in the object place recognition test (OPR). Compared with the ND group, the HFD-fed mice showed Tau hyperphosphorylation at ps214 in the hippocampus and at ps422 and ps396 in the cortex, which was accompanied by GSK-3β activation. The higher activated phenotype of microglia in the brain of the HFD group was typically evidenced by an increased average area of the cell body and reduced complexity of microglial processes. Immunoblotting showed that long-term HFD intake augmented the levels of inflammatory cytokines IL-6 in the hippocampus. These findings indicate that long-term HFD intake deteriorates cognitive dysfunctions, accompanied by Tau hyperphosphorylation, microglial activation, and inflammatory cytokine expression, and that the modifiable lifestyle factor contributes to the cognitive decline of senior citizens. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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24 pages, 5623 KiB

Open AccessArticle

Moringa Oleifera Alleviates Aβ Burden and Improves Synaptic Plasticity and Cognitive Impairments in APP/PS1 Mice

by Yacoubou Abdoul Razak Mahaman, Jun Feng, Fang Huang, Maibouge Tanko Mahamane Salissou, Jianzhi Wang, Rong Liu, Bin Zhang, Honglian Li, Feiqi Zhu and Xiaochuan Wang

Nutrients 2022, 14(20), 4284; https://doi.org/10.3390/nu14204284 - 14 Oct 2022

Cited by 17 | Viewed by 3816

Abstract

Alzheimer’s disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Aβ and Tau, and the multifactorial etiology of AD, there is now more and more interest [...] Read more.

Alzheimer’s disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Aβ and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues. In this study, we treated APP/PS1 mice with a methanolic extract of MO for four months and evaluated its effect on AD-related pathology in these mice using a multitude of behavioral, biochemical, and histochemical tests. Our data revealed that MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments. MO treatment abrogated the Aβ burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels. Moreover, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice. MO is a nutraceutical agent with promising therapeutic potential that can be used in the management of AD and other neurodegenerative diseases. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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20 pages, 5462 KiB

Open AccessArticle

Fatty Acid-Derived N-acylethanolamines Dietary Supplementation Attenuates Neuroinflammation and Cognitive Impairment in LPS Murine Model

by Anna Tyrtyshnaia, Sophia Konovalova, Arina Ponomarenko, Anastasia Egoraeva and Igor Manzhulo

Nutrients 2022, 14(18), 3879; https://doi.org/10.3390/nu14183879 - 19 Sep 2022

Cited by 7 | Viewed by 2966

Abstract

Neuroinflammation plays a critical role in the pathogenesis of most neurological and neurodegenerative diseases and therefore represents a potential therapeutic target. In this regard, accelerating the resolution process in chronic neuroinflammation may be an effective strategy to deal with the cognitive consequences of [...] Read more.

Neuroinflammation plays a critical role in the pathogenesis of most neurological and neurodegenerative diseases and therefore represents a potential therapeutic target. In this regard, accelerating the resolution process in chronic neuroinflammation may be an effective strategy to deal with the cognitive consequences of neuropathology and generalized inflammatory processes. N-acylethanolamine (NAE) derivatives of fatty acids, being highly active lipid mediators, possess pro-resolving activity in inflammatory processes and are promising agents for the suppression of neuroinflammation and its consequences. This paper is devoted to a study of the effects played by dietary supplement (DS), containing a composition of fatty acid-derived NAEs, obtained from squid Berryteuthis magister, on the hippocampal neuroinflammatory and memory processes. By detecting the production of pro-inflammatory cytokines and glial markers, a pronounced anti-inflammatory activity of DS was demonstrated both in vitro and in vivo. DS administration reversed the LPS-induced reduction in hippocampal neurogenesis and memory deterioration. LC-MS analysis revealed an increase in the production of a range of NAEs with well-documented anti-inflammatory activity in response to the administered lipid composition. To conclude, we found that tested DS suppresses the neuroinflammatory response by reducing glial activation, positively regulates neural progenitor proliferation, and attenuates hippocampal-dependent memory impairment. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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26 pages, 3164 KiB

Open AccessArticle

A High-Fat Diet Modifies Brain Neurotransmitter Profile and Hippocampal Proteome and Morphology in an IUGR Pig Model

by Natalia Yeste, Jorge Pérez-Valle, Ana Heras-Molina, José Luis Pesántez-Pacheco, Esteban Porrini, Antonio González-Bulnes and Anna Bassols

Nutrients 2022, 14(16), 3440; https://doi.org/10.3390/nu14163440 - 22 Aug 2022

Cited by 2 | Viewed by 2467

Abstract

Intrauterine Growth Restriction (IUGR) hinders the correct growth of the fetus during pregnancy due to the lack of oxygen or nutrients. The developing fetus gives priority to brain development (“brain sparing”), but the risk exists of neurological and cognitive deficits at short or [...] Read more.

Intrauterine Growth Restriction (IUGR) hinders the correct growth of the fetus during pregnancy due to the lack of oxygen or nutrients. The developing fetus gives priority to brain development (“brain sparing”), but the risk exists of neurological and cognitive deficits at short or long term. On the other hand, diets rich in fat exert pernicious effects on brain function. Using a pig model of spontaneous IUGR, we have studied the effect on the adult of a long-term high-fat diet (HFD) on the neurotransmitter profile in several brain areas, and the morphology and the proteome of the hippocampus. Our hypothesis was that animals affected by IUGR (born with low birth weight) would present a different susceptibility to an HFD when they become adults, compared with normal birth-weight animals. Our results indicate that HFD affected the serotoninergic pathway, but it did not provoke relevant changes in the morphology of the hippocampus. Finally, the proteomic analysis revealed that, in some instances, NBW and LBW individuals respond to HFD in different ways. In particular, NBW animals presented changes in oxidative phosphorylation and the extracellular matrix, whereas LBW animals presented differences in RNA splicing, anterograde and retrograde transport and the mTOR pathway. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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16 pages, 4425 KiB

Open AccessArticle

Quercetin Increases Mitochondrial Biogenesis and Reduces Free Radicals in Neuronal SH-SY5Y Cells

by Chia-Ling Ho, Ning-Jo Kao, Ching-I Lin, Tzu-Wen L. Cross and Shyh-Hsiang Lin

Nutrients 2022, 14(16), 3310; https://doi.org/10.3390/nu14163310 - 12 Aug 2022

Cited by 24 | Viewed by 2951

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disorder that causes dementia and affects millions of people worldwide. The mechanism underlying AD is unclear; however, oxidative stress and mitochondrial biogenesis have been reported to be involved in AD progression. Previous research has also reported [...] Read more.

Alzheimer’s disease (AD) is a common neurodegenerative disorder that causes dementia and affects millions of people worldwide. The mechanism underlying AD is unclear; however, oxidative stress and mitochondrial biogenesis have been reported to be involved in AD progression. Previous research has also reported the reduction in mitochondrial biogenesis in the brains of patients with AD. Quercetin (QE), a type of polyphenol, has been found to be capable of increasing mitochondrial biogenesis in the body. Accordingly, we explored whether QE could reduce amyloid beta (Aβ) accumulation caused by hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y cells. Our results revealed that QE stimulated the expression of mitochondrial-related proteins such as SIRT1, PGC-1α, and TFAM and subsequently activated mitochondrial biogenesis. Additionally, QE increased ADAM10 expression but reduced H₂O₂-induced reactive oxygen species production, apoptosis, β-site amyloid precursor protein cleaving enzyme 1 expression, and Aβ accumulation in the SH-SY5Y cells. These findings indicate that QE can effectively elevate mitochondrial biogenesis-related proteins and reduce the damage caused by oxidative stress, making it a promising option for protecting neuronal cells. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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16 pages, 3407 KiB

Open AccessEditor’s ChoiceArticle

Probiotic Bifidobacterium breve MCC1274 Mitigates Alzheimer’s Disease-Related Pathologies in Wild-Type Mice

by Mona Abdelhamid, Chunyu Zhou, Cha-Gyun Jung and Makoto Michikawa

Nutrients 2022, 14(12), 2543; https://doi.org/10.3390/nu14122543 - 19 Jun 2022

Cited by 24 | Viewed by 4681

Abstract

Probiotics improve brain function, including memory and cognition, via the microbiome–gut–brain axis. Oral administration of Bifidobacterium breve MCC1274 (B. breve MCC1274) improves cognitive function in App^NL-G-F mice and mild cognitive impairment (MCI) subjects, and mitigates Alzheimer’s disease (AD)-like pathologies. However, its [...] Read more.

Probiotics improve brain function, including memory and cognition, via the microbiome–gut–brain axis. Oral administration of Bifidobacterium breve MCC1274 (B. breve MCC1274) improves cognitive function in App^NL-G-F mice and mild cognitive impairment (MCI) subjects, and mitigates Alzheimer’s disease (AD)-like pathologies. However, its effects on wild-type (WT) mice have not yet been explored. Thus, the effects of B. breve MCC1274 on AD-like pathologies in two-month-old WT mice were investigated, which were orally administered B. breve MCC1274 for four months. Aβ levels, amyloid precursor protein (APP), APP processing enzymes, phosphorylated tau, synaptic protein levels, glial activity, and cell proliferation in the subgranular zone of the dentate gyrus were evaluated. Data analysis was performed using Student’s t-test, and normality was tested using the Shapiro–Wilk test. Oral administration of B. breve MCC1274 in WT mice decreased soluble hippocampal Aβ42 levels by reducing presenilin1 protein levels, and reduced phosphorylated tau levels. It also activated the protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway, which may be responsible for the reduction in presenilin1 levels and inhibition of tau phosphorylation. B. breve MCC1274 supplementation attenuated microglial activation and elevated synaptic protein levels in the hippocampus. These findings suggest that B. breve MCC1274 may mitigate AD-like pathologies in WT mice by decreasing Aβ42 levels, inhibiting tau phosphorylation, attenuating neuroinflammation, and improving synaptic protein levels. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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17 pages, 3127 KiB

Open AccessEditor’s ChoiceArticle

Lactobacillus paracasei CCFM1229 and Lactobacillus rhamnosus CCFM1228 Alleviated Depression- and Anxiety-Related Symptoms of Chronic Stress-Induced Depression in Mice by Regulating Xanthine Oxidase Activity in the Brain

by Mengshu Xu, Peijun Tian, Huiyue Zhu, Renying Zou, Jianxin Zhao, Hao Zhang, Gang Wang and Wei Chen

Nutrients 2022, 14(6), 1294; https://doi.org/10.3390/nu14061294 - 18 Mar 2022

Cited by 27 | Viewed by 5836

Abstract

Depression is a common mood disorder that affects around 350 million people worldwide. We studied the effect of supplementation with Lactobacillus strains for the treatment of depression. Except for control group (n = 8), C57BL/6J mice were treated with Lactobacillus during six [...] Read more.

Depression is a common mood disorder that affects around 350 million people worldwide. We studied the effect of supplementation with Lactobacillus strains for the treatment of depression. Except for control group (n = 8), C57BL/6J mice were treated with Lactobacillus during six weeks of chronic unpredictable stress (depression group: n = 9, Lactobacillus intervention group: n = 7). L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly reduced depressive behaviour in the forced swimming test and tail suspension test, significantly reduced anxiety behaviour in the open field test, and reduced anxiety behaviour in the marble burying test and light/dark box test. L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly increased the brain serotonin and brain-derived neurotrophic factor concentrations, and CCFM1229 significantly decreased the serum corticosterone concentration, all of which are closely associated with the relief of depressive symptoms. Furthermore, CCFM1229 and CCFM1228 were shown to regulate purine metabolism in mice, as indicated by decreases in brain xanthine oxidase activity and an increase in liver adenosine deaminase activity. Anxiety- and depression-related indicators were significantly associated with xanthine oxidase activity in the cerebral cortex. The strains CCFM1229 and CCFM1228 reduced anxiety- and depression-related behaviour in a mouse model of chronic stress-induced depression, which may be achieved by regulating the activity of brain xanthine oxidase. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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21 pages, 3871 KiB

Open AccessArticle

Regulatory Effects of Quercetin on M1/M2 Macrophage Polarization and Oxidative/Antioxidative Balance

by Cheng-Fang Tsai, Guan-Wei Chen, Yen-Chang Chen, Ching-Kai Shen, Dah-Yuu Lu, Liang-Yo Yang, Jia-Hong Chen and Wei-Lan Yeh

Nutrients 2022, 14(1), 67; https://doi.org/10.3390/nu14010067 - 24 Dec 2021

Cited by 128 | Viewed by 11553

Abstract

Macrophage polarization plays essential and diverse roles in most diseases, such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Homeostasis dysfunction in M1/M2 macrophage polarization causes pathological conditions and inflammation. Neuroinflammation is characterized by microglial activation and the concomitant production of pro-inflammatory cytokines, [...] Read more.

Macrophage polarization plays essential and diverse roles in most diseases, such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Homeostasis dysfunction in M1/M2 macrophage polarization causes pathological conditions and inflammation. Neuroinflammation is characterized by microglial activation and the concomitant production of pro-inflammatory cytokines, leading to numerous neurodegenerative diseases and psychiatric disorders. Decreased neuroinflammation can be obtained by using natural compounds, including flavonoids, which are known to ameliorate inflammatory responses. Among flavonoids, quercetin possesses multiple pharmacological applications and regulates several biological activities. In the present study, we found that quercetin effectively inhibited the expression of lipocalin-2 in both macrophages and microglial cells stimulated by lipopolysaccharides (LPS). The production of nitric oxide (NO) and expression levels of the pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, were also attenuated by quercetin treatment. Our results also showed that quercetin significantly reduced the expression levels of the M1 markers, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, in the macrophages and microglia. The M1 polarization-associated chemokines, C–C motif chemokine ligand (CCL)-2 and C-X-C motif chemokine ligand (CXCL)-10, were also effectively reduced by the quercetin treatment. In addition, quercetin markedly reduced the production of various reactive oxygen species (ROS) in the microglia. The microglial phagocytic ability induced by the LPS was also effectively reduced by the quercetin treatment. Importantly, the quercetin increased the expression levels of the M2 marker, IL-10, and the endogenous antioxidants, heme oxygenase (HO)-1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase-1 (NQO1). The enhancement of the M2 markers and endogenous antioxidants by quercetin was activated by the AMP-activated protein kinase (AMPK) and Akt signaling pathways. Together, our study reported that the quercetin inhibited the effects of M1 polarization, including neuroinflammatory responses, ROS production, and phagocytosis. Moreover, the quercetin enhanced the M2 macrophage polarization and endogenous antioxidant expression in both macrophages and microglia. Our findings provide valuable information that quercetin may act as a potential drug for the treatment of diseases related to inflammatory disorders in the central nervous system. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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15 pages, 1943 KiB

Open AccessArticle

Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction

by Vesna Tesic, Jelena Ciric, Irena Jovanovic Macura, Nevena Zogovic, Desanka Milanovic, Selma Kanazir and Milka Perovic

Nutrients 2021, 13(12), 4526; https://doi.org/10.3390/nu13124526 - 17 Dec 2021

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Abstract

Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious [...] Read more.

Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats. Corticosterone level was increased in the cortex of aged ad libitum-fed rats. Food restriction induced its further increase, accompanied with an increase in the level of 11β-hydroxysteroid dehydrogenase type 1. However, alterations in the level of GR phosphorylated at Ser²³² were not detected in animals on food restriction, in line with unaltered CDK5 level, the decrease of Hsp90, and an increase in a negative regulator of GR function, FKBP51. Moreover, our data revealed that reduced food intake prevented age-related increase in the levels of NFκB, gfap, and bax, confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of c-fos, our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors

by Rut Fadó, Anna Molins, Rocío Rojas and Núria Casals

Nutrients 2022, 14(19), 4137; https://doi.org/10.3390/nu14194137 - 5 Oct 2022

Cited by 17 | Viewed by 10578

Abstract

In recent decades, traditional eating habits have been replaced by a more globalized diet, rich in saturated fatty acids and simple sugars. Extensive evidence shows that these dietary factors contribute to cognitive health impairment as well as increase the incidence of metabolic diseases [...] Read more.

In recent decades, traditional eating habits have been replaced by a more globalized diet, rich in saturated fatty acids and simple sugars. Extensive evidence shows that these dietary factors contribute to cognitive health impairment as well as increase the incidence of metabolic diseases such as obesity and diabetes. However, how these nutrients modulate synaptic function and neuroplasticity is poorly understood. We review the Western, ketogenic, and paleolithic diets for their effects on cognition and correlations with synaptic changes, focusing mainly (but not exclusively) on animal model studies aimed at tracing molecular alterations that may contribute to impaired human cognition. We observe that memory and learning deficits mediated by high-fat/high-sugar diets, even over short exposure times, are associated with reduced arborization, widened synaptic cleft, narrowed post-synaptic zone, and decreased activity-dependent synaptic plasticity in the hippocampus, and also observe that these alterations correlate with deregulation of the AMPA-type glutamate ionotropic receptors (AMPARs) that are crucial to neuroplasticity. Furthermore, we explored which diet-mediated mechanisms modulate synaptic AMPARs and whether certain supplements or nutritional interventions could reverse deleterious effects, contributing to improved learning and memory in older people and patients with Alzheimer’s disease. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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27 pages, 495 KiB

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The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

by Angelica Varesi, Elisa Pierella, Marcello Romeo, Gaia Bavestrello Piccini, Claudia Alfano, Geir Bjørklund, Abigail Oppong, Giovanni Ricevuti, Ciro Esposito, Salvatore Chirumbolo and Alessia Pascale

Nutrients 2022, 14(3), 668; https://doi.org/10.3390/nu14030668 - 5 Feb 2022

Cited by 117 | Viewed by 17465

Abstract

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain [...] Read more.

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease. Full article

(This article belongs to the Special Issue The Impact of Nutrition on Brain Metabolism and Disease)

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