Nutritional Neuroscience最新文献

Objective: Targeting the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway represents a promising therapeutic strategy for multiple sclerosis (MS). However, approved drugs like dimethyl fumarate (DMF) often induce severe side effects. This study investigated the natural flavonoid luteolin (LUT) as a potential dietary supplement alternative to DMF in a cuprizone (CPZ)-induced demyelination mouse model of MS.Methods: Mice were randomly assigned to five groups: control, CPZ model, CPZ+DMF (15 mg/kg), CPZ+LUT (25 mg/kg), and CPZ+LUT (50 mg/kg). Motor coordination and spatial memory were assessed via rotarod and Morris water maze tests. Myelin integrity was evaluated by Luxol fast blue staining and myelin basic protein (MBP) immunofluorescence/Western blot. Oxidative stress was measured by assessing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) levels. Nrf2 pathway activation was analyzed by nuclear translocation of Nrf2 and expression of downstream proteins (HO-1, NQO1) via Western blot. Molecular docking simulated interactions between compounds and the Keap1 protein.Results: LUT treatment significantly restored motor coordination and spatial memory, with efficacy comparable to DMF. It promoted MBP expression, attenuated oxidative damage by modulating SOD, CAT, GSH-Px, and MDA levels, and preserved myelin integrity. Furthermore, LUT markedly facilitated Nrf2 nuclear translocation and upregulated HO-1 and NQO1 expression. Molecular docking indicated that LUT possessed stronger binding affinity to the target protein Keap1 and a lower potential for off-target toxicity compared to the primary active metabolite of DMF.Conclusion: Luteolin exerts significant neuroprotective effects, primarily via Nrf2 pathway activation, with efficacy parallel to DMF but a superior safety profile. These findings identify LUT as a promising natural compound, bridging functional foods and MS therapy, and provide a foundation for developing LUT-enriched dietary regimens as an adjunct treatment strategy for MS.

Objectives: This study, using the Youth Risk Behavior Surveillance Survey 2021 (YRBS 2021) focused on exploring the sex differences in the associations between sugar-sweetened beverages (SSB) (soda and sports drinks) and cognitive difficulties (memory, concentration, and decision-making); as well as the mediation effect of sleep on the associations.

Methods: 8,229 from the YRBS 2021 data were included in the study. SSB consumption was treated as a continuous variable with various levels of frequencies, as well as coded as a categorical variable with three levels (non-drinker, non-daily drinker, and daily drinker). Cognitive difficulty was a binary variable. Sleep was treated as a continuous variable with durations of hours. Regression models and bootstrapping methods were used in this study.

Results: Compared to non-drinkers, increased odds of cognitive difficulties were observed in girls (OR: 1.49; 95% CI: 1.18-1.87) and boys soda daily-drinkers (OR: 1.53; 95% CI: 1.24-1.87); and girls sports-drink daily-drinkers (OR: 1.39; 95% CI: 1.08-1.80). Sleep, as a mediator, affected the associations of overall SSB consumption (βs = .01; p < .001) and soda consumption (βs = .02; p < .001) with cognitive difficulties among boys and girls; as well as the path between sports drink consumption and cognitive difficulties in boys (β = .01; p < .001).

Discussion: SSB consumption is associated with both shorter sleep duration and greater cognitive difficulties among adolescents, with sleep acting as a meaningful pathway linking consumption to cognitive functioning. Reducing SSB intake and promoting healthier behaviors may improve both sleep and cognitive health in youth.

Objective: Epilepsy treatments often lead to vitamin D (VitD) deficiency. Although vitamin D₃ (VitD₃) has been shown to reduce epileptic symptoms by 43%, its preventive effects remain unclear. This study investigated the potential of VitD pretreatment in two common acute epilepsy mouse models and explored its effects on seizure severity, latency, and molecular mechanisms involving calcium-sensing receptor (CaSR), phosphatase and tensin homolog (PTEN), and autophagy.

Methods: Mice were randomly divided into nine groups (n = 15). VitD or vehicle was administered 40 min before pentylenetetrazole (PTZ) or kainic acid (KA) given intraperitoneal injection (i.p). Seizure behavior and electroencephalograms (EEGs) were recorded for 60 min. After 24 h, hippocampal tissues were analyzed histologically and assessed for expression of autophagy-related proteins, CaSR, and PTEN.

Results: Both PTZ and KA induced acute seizures (Racine Grade IV+), with corresponding high-amplitude EEG spikes, neuronal damage, and mossy fiber sprouting. CaSR and autophagy markers were upregulated, while PTEN was downregulated, especially in the KA group. VitD pretreatment reduced seizure frequency, prolonged latency, alleviated hippocampal damage, downregulated CaSR and autophagy markers, and upregulated PTEN. These effects were milder than those of valproate. Combined VitD and Oroxin B treatment further improved outcomes.

Conclusions: (1) PTZ-induced seizures increased CaSR and decreased PTEN, triggering autophagy and worsening symptoms. (2) KA-induced epilepsy caused more severe damage with stronger autophagy activation. (3) VitD pretreatment mitigated seizures by modulating CaSR, PTEN, and autophagy, showing greater efficacy in the PTZ model.

Background: This study assessed whether dietary medium-chain triglyceride (MCT) supplementation improves outcomes in acute severe encephalopathy patients within a Neurological Intensive Care Unit (NICU).

Methods: A single-center, double-blind, randomized trial was conducted at The Third Affiliated Hospital of Sun Yat-sen University (May 2021 - August 2023). Forty-six patients were randomized to MCT supplementation (n = 23) or control (n = 23). Primary outcomes were 180-day poor neurologic outcome (modified Rankin Scale score >4) and all-cause mortality. Secondary outcomes included coma duration, mechanical ventilation duration, ICU length of stay, and hospital costs. Final follow-up was May 1, 2024.

Results: At 180 days, poor neurologic outcome occurred in 26.1% (6/23) of the MCT group versus 56.5% (13/23) of controls (RR 0.27; 95% CI 0.08-0.94; P < 0.05). All-cause mortality was 13.0% (MCT) vs. 30.4% (control) (RR 0.43; 95% CI 0.13-1.46; P > 0.05). The MCT group showed significant improvements in all secondary outcomes: shorter coma duration (8.4 vs 13.2 days; P < 0.05), reduced mechanical ventilation (55.0 vs 154.9 h; P < 0.05), shorter ICU stay (13.4 vs 19.3 days; P < 0.05), and lower hospital costs (¥76,000 vs ¥100,200; P < 0.05).

Conclusions: MCT supplementation significantly reduced poor neurologic outcomes at 180 days in acute severe encephalopathy patients. It also significantly shortened coma duration, mechanical ventilation time, ICU stay, and lowered hospital costs. Mortality reduction was not statistically significant.

Background: Periodontitis is associated with poorer cognitive function. It remains unclear whether folate plays a crucial role in periodontitis-promoted cognitive impairment (CI) in the elderly population.

Methods: Data for this cross-sectional population-based study were obtained from the National Health and Nutrition Examination Survey (NHANES), 2011-2014 database. Associations between periodontitis and cognitive scores, exogenous folate (dietary intake folate equivalents and dietary supplement folate), and endogenous folate (folate from serum and red blood cells) levels were estimated by propensity score weighted regression models. Natural effect models were applied to estimate the mediation effect of folate for the periodontitis-cognition relationship.

Results: Out of the 1966 participants, 869 (44.2%) had periodontitis. The periodontitis group has lower cognitive scores and dietary supplement, serum total, and RBC folate levels. The mediation effect of dietary supplement folate for the periodontitis-general cognition score association was significant, with mediation proportions of 8.4%. The mediation effects of serum total folate and RBC folate for periodontitis-general cognition score were both significant, with mediation proportions of 9.1%. Notably, periodontitis cases with dietary supplement folate or high dietary intake folate had significantly higher general cognition scores than those of periodontitis cases without dietary supplement folate or with low dietary intake folate.

Conclusions: Dietary folate supplementation may serve as a modifiable strategy to slow periodontitis-related cognitive decline in older adults, with serum and RBC levels functioning as key biomarkers of its potential effect.

Introduction: Parkinson's disease (PD) is a progressive, age-associated neurodegenerative disorder characterized by loss of nigrostriatal dopaminergic neurons, leading to motor and non-motor dysfunctions. Central to PD pathogenesis are dysregulated protein kinases, such as LRRK2, PINK1, GSK-3β, and CDK5, that govern neuroinflammation, autophagy impairment, oxidative stress, mitochondrial dysfunction, and α-synuclein aggregation.

Objective: To critically assess the potential of phytoconstituents as modulators of key protein kinases in PD.

Methods: A comprehensive literature review was carried out with PubMed, SCOPUS, SciDirect, Google Scholar, Hindawi, clinicaltrials.gov, and Wiley Online Library, integrating data from in silico, in vitro, and in vivo studies focused on the potential role of phytoconstituents in kinase modulation.

Results: Preclinical studies consistently demonstrate that flavonoids, polyphenols, and alkaloids mitigate oxidative stress, restore mitochondrial function, inhibit apoptotic signaling, and reduce α-synuclein aggregation via modulation of LRRK2, GSK-3β, CDK5, and related protein kinases. In silico analyses reveal favorable binding affinities to kinase domains, while network pharmacology suggests synergistic multi-kinase effects. These insights align with challenges observed in translational trials of small-molecule kinase inhibitors, particularly regarding bioavailability and target selectivity.

Conclusion: While current PD therapies focus on symptomatic relief, targeting protein kinases with phytoconstituents presents a promising disease-modifying approach. Future research should prioritize clinical validation and mechanistic studies to establish their therapeutic potential, paving the way for novel kinase-targeted interventions in PD management.Trial registration: ClinicalTrials.gov identifier: NCT02281474.Trial registration: ClinicalTrials.gov identifier: NCT02954978.Trial registration: ClinicalTrials.gov identifier: NCT02970019.Trial registration: ClinicalTrials.gov identifier: NCT03445338.Trial registration: ClinicalTrials.gov identifier: NCT03655236.Trial registration: ClinicalTrials.gov identifier: NCT04691661.Trial registration: ClinicalTrials.gov identifier: NCT04551534.Trial registration: ClinicalTrials.gov identifier: NCT03710707.Trial registration: ClinicalTrials.gov identifier: NCT04557800.Trial registration: ClinicalTrials.gov identifier: NCT04056689.Trial registration: ClinicalTrials.gov identifier: NCT03205488.Trial registration: ClinicalTrials.gov identifier: NCT05348785.

Objectives: Painful diabetic neuropathy poses a devastating health burden, with one-third of diabetic patients being afflicted. Currently, most of the neuropathic pain drugs have shown insufficient efficacy, significant adverse reactions and poor patient compliance. Striving for improved neuropathic pain therapies is necessary in diabetic patients. This study aimed to investigate the potential antinociceptive effect of eupatilin, a natural flavonoid, against persistent neuropathic pain associated with diet-induced type 2 diabetes, and probe mechanism(s).Methods: C57BL6J male mice were fed with a high-fat diet for 8 weeks to induce type 2 diabetes. The von Frey test and the acetone test were used to assess pain-like behaviors, shown as neuropathic allodynia to mechanical and cold stimuli, respectively. Redox and bioenergetics-related mechanisms were investigated in vivo and in vitro.Results: Chronic eupatilin therapy not only ameliorated the established symptoms of mechanical and cold allodynia in mice with type 2 diabetes, but also decelerated pain development given preemptively at low doses. Although eupatilin did not impact metabolic features (body weight, food intake, blood glucose, glucose tolerance, glycosylated haemoglobin and insulin) in diabetic mice, it improved mitochondrial bioenergetics in dorsal root ganglion neurons, alleviated exacerbated oxidative stress in pain-associated tissues, and restored nerve conduction velocity and blood flow in sciatic nerves. Notably, the pain-alleviating actions of eupatilin were modified by pharmacologically manipulating mitochondrial bioenergetics and redox status.Discussion: These findings uncover the analgesic activity of eupatilin, an effect that suggests a causal association with its bioenergetics-enhancing and antioxidant effects, in mice with diet-induced type 2 diabetes.

Objectives: To evaluate vitamin B1 in alcohol-induced headaches and elucidate its underlying mechanisms and potential preventive applications.

Methods: In vitro cellular assays assessed the cytotoxicity of alcohol and the protective effects of vitamin B1 on components of the mouse neurovascular units, including endothelial cells, astrocytes, and neurons. Murine models were used to study the effects of alcohol on cerebral blood flow and neurons, as well as the neuroprotective efficacy of vitamin B1. Behavioral tests, immunohistochemistry staining, and two-photon microscope imaging were utilized to quantify physiological and histological changes.

Results: Alcohol demonstrated selective toxicity to hippocampal neurons, distinct from other components of the neurovascular units. It disrupted the dynamics of cerebral blood flow, leading to hypoxic neuronal death. Alcohol's influence on neuron cells contributes to headache pathogenesis. Vitamin B1 significantly attenuated ethanol-mediated cerebral blood flow dysregulation and neuronal damage by reducing reactive oxygen species levels, thereby ameliorating headache-related symptoms.

Discussion: These findings provide new insights into the pathogenesis of alcohol-related headaches and propose vitamin B1 as a viable prophylactic intervention.

Background: Current researches suggest that the microbiota-gut-brain axis plays a critical role in modulating human cognition and emotion, particularly in the context of psychiatric disorders. Probiotic fermented dairy products have been shown to regulate gut microbiota composition and alleviate depressive symptoms; however, the underlying mechanism and associated metabolic pathways remain unclear.Methods: In this study, we compared the effects of probiotics (Lactobacillus reuteri and Lactobacillus bulgaricus) fermented yogurt on chronic unpredictable mild stress (CUMS)-induced anxious and depressive-like symptoms in mice, as well as discussed potential mechanisms.Results: Behavioral tests revealed that both L. reuteri and L. bulgaricus fermented yogurt significantly alleviated these symptoms. We also observed that Lactobacillus fermented yogurt exerted an overall neuroprotective effect in the hippocampus and helped maintain normal cerebral activity. L. reuteri and L. bulgaricus fermented yogurts were also observed to ameliorate the levels of monoamine neurotransmitters and inflammatory cytokines via inhibiting the activation of the NF-κB pathway accompanied by elevating the CREB-BDNF pathway.Conclusion: Our findings suggest that L. reuteri and L. bulgaricus fermented yogurts may modulate gut microbiota composition and host metabolism, thereby performing neuroprotective effects and ameliorating depressive behaviors in mice by at least partially microbiota-gut-brain axis. These findings have important implications for understanding the antidepressant mechanisms of fermented dairy products that target the intestinal microbiota and provide a promising new way for the development of novel treatments for depression.

Background: Different intermittent fasting (IF) regimens have been used in healthy individuals to improve body composition; however, other potential benefits or harm, such as modulation of behaviours, are little studied in healthy populations. The present study aimed to evaluate the influence of different IF regimens on parameters related to the behavioural and cerebral aspects in healthy rats and compare them to caloric restriction.

Methods: Adult Wistar rats were randomised into five groups: control (CON); caloric restriction (CR); time-restricted feeding (TRF); alternate-day fasting (ADF); and alternate-day modified fasting (ADMF), and then evaluated during four weeks.

Results: The ADF and ADMF groups had the lowest weight over the weeks and decreased depressive-like behaviour, while TRF decreased anxiety-like behaviour. However, all experimental groups presented some damage in the brain tissues (central cortex and hippocampus), and ADF had the largest area of ⁣⁣NF-κB marking.

Conclusion: Although all groups submitted to IF showed benefits in behaviour, they also presented damage to brain tissues (gemistocystic astrocytes, and ischemic neuronal cell bodies).