Objectives: Postnatal epilepsy often arises after periventricular leukomalacia (PVL) in preterm infants and resists to treatment. Its underlying mechanisms and potential preventive strategies remain unclear. Probiotics, known to alleviate microbial dysbiosis and reduce inflammation, may offer therapeutic benefits.Methods: PVL injure was conducted using a combination of hypoxia-ischemia and lipopolysaccharide treatment. The rats were evaluated for seizure susceptibility, neuroinflammation, GABAergic neurons, and gut microbiota composition before and after probiotic administration. The probiotic formulation included Lactobacillus rhamnosus, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum and Bifidobacterium breve in galacto-oligosaccharide and Fructooligosaccharides.Results: PVL rats exhibited microgliosis, reduced density of premyelinating oligodendrocytes, and decreased myelin expression (all P < 0.05). At postnatal days 85-90, these rats showed a significantly higher frequency of electrographic seizures and longer total seizure duration (P < 0.05). A significant reduction in cortical GABAergic neurons, particularly somatostatin-positive interneurons, was also observed in PVL rats compared to controls (P < 0.01). Treatment with probiotics restored GABAergic neurons and significantly reduced seizure frequency and duration (P < 0.05). Additionally, probiotics modulated gut microbiota composition and increased levels of butyric acid in both fecal samples and cerebrospinal fluid (CSF) (P < 0.05). Probiotic treatment also reduced cortical microglial activation and lowered CSF levels of the proinflammatory cytokine TNF-α.Conclusion: Probiotic supplementation may reduce seizure activity following PVL brain injury by mitigating neuroinflammation and restoring GABAergic neurons via the gut-brain axis. These findings suggest that probiotics could serve as a promising adjuvant therapy for preventing epilepsy after PVL.
目的:早产儿脑室周围白质软化(PVL)后常发生产后癫痫,且对治疗有抵抗性。其潜在机制和潜在的预防策略尚不清楚。众所周知,益生菌可以缓解微生物生态失调和减少炎症,可能提供治疗益处。方法:采用低氧缺血联合脂多糖治疗PVL损伤。在给予益生菌前后评估大鼠的癫痫易感性、神经炎症、gaba能神经元和肠道微生物群组成。益生菌配方包括鼠李糖乳杆菌、干酪乳杆菌、两歧双歧杆菌、乳酸双歧杆菌、长双歧杆菌和短双歧杆菌中的半乳糖低聚糖和低聚果糖。结果:PVL大鼠表现出小胶质细胞增生,髓鞘前少突胶质细胞密度降低,髓鞘表达降低(均为P P P P P P)结论:补充益生菌可能通过减轻神经炎症和通过肠-脑轴恢复gaba能神经元来减少PVL脑损伤后的癫痫发作活动。这些发现表明益生菌可以作为一种有希望的辅助治疗预防PVL后癫痫。
{"title":"Probiotics restore GABAergic neurons and attenuate postnatal seizures in periventricular leukomalacia.","authors":"Jia-Shing Chen, Ming-Jung Tu, Yu-Ming Chang, Yi-Fang Tu, Chi-Wu Chiang","doi":"10.1080/1028415X.2025.2574964","DOIUrl":"https://doi.org/10.1080/1028415X.2025.2574964","url":null,"abstract":"<p><p><b>Objectives:</b> Postnatal epilepsy often arises after periventricular leukomalacia (PVL) in preterm infants and resists to treatment. Its underlying mechanisms and potential preventive strategies remain unclear. Probiotics, known to alleviate microbial dysbiosis and reduce inflammation, may offer therapeutic benefits.<b>Methods:</b> PVL injure was conducted using a combination of hypoxia-ischemia and lipopolysaccharide treatment. The rats were evaluated for seizure susceptibility, neuroinflammation, GABAergic neurons, and gut microbiota composition before and after probiotic administration. The probiotic formulation included Lactobacillus rhamnosus, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum and Bifidobacterium breve in galacto-oligosaccharide and Fructooligosaccharides.<b>Results:</b> PVL rats exhibited microgliosis, reduced density of premyelinating oligodendrocytes, and decreased myelin expression (all <i>P</i> < 0.05). At postnatal days 85-90, these rats showed a significantly higher frequency of electrographic seizures and longer total seizure duration (<i>P</i> < 0.05). A significant reduction in cortical GABAergic neurons, particularly somatostatin-positive interneurons, was also observed in PVL rats compared to controls (<i>P</i> < 0.01). Treatment with probiotics restored GABAergic neurons and significantly reduced seizure frequency and duration (<i>P</i> < 0.05). Additionally, probiotics modulated gut microbiota composition and increased levels of butyric acid in both fecal samples and cerebrospinal fluid (CSF) (<i>P</i> < 0.05). Probiotic treatment also reduced cortical microglial activation and lowered CSF levels of the proinflammatory cytokine TNF-α.<b>Conclusion:</b> Probiotic supplementation may reduce seizure activity following PVL brain injury by mitigating neuroinflammation and restoring GABAergic neurons via the gut-brain axis. These findings suggest that probiotics could serve as a promising adjuvant therapy for preventing epilepsy after PVL.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1080/1028415X.2025.2582520
Rajashri Kulal, Mohammed Touseef Khan, Babasaheb Bhaskarrao Borse, Muthukumar Serva Peddha
Depression affects millions globally, prompting the search for novel treatments. Natural compounds like spice oleoresins show promise due to their bioactive constituents. This study explores the use of Hydroxypropyl-beta-cyclodextrin (HPBCD) for nano-encapsulation to enhance the efficacy of pepper, turmeric, and chilli oleoresins in alleviating depression in a mice model. Chronic unpredictable mild stress (CUMS) was induced for 28 days, followed by administering nano-encapsulated oleoresins (25 mg/kg). Behavioural analyses revealed improved activity, while neurochemical studies showed increased serotonin and dopamine levels with reduced monoamine oxidase (MAO) activity. Western blot highlighted changes in BDNF, supported by histopathological evidence of neuroprotection. Biochemical assays indicated reduced oxidative stress, acetylcholinesterase activity, and enhanced catalase and superoxide dismutase levels. 16S rRNA sequencing revealed improved gut microbiota, with increased beneficial bacteria. Notably, nano-encapsulated chilli oleoresin exhibited the highest efficacy. These findings support the multi-targeted potential of nano-encapsulated spice oleoresins as complementary treatments for depression, addressing neurobiological and gut-related factors.
{"title":"Effect of encapsulated spice oleoresins on chronic unpredictable mild stress-induced depression and gut microbiome modulation in mice model.","authors":"Rajashri Kulal, Mohammed Touseef Khan, Babasaheb Bhaskarrao Borse, Muthukumar Serva Peddha","doi":"10.1080/1028415X.2025.2582520","DOIUrl":"https://doi.org/10.1080/1028415X.2025.2582520","url":null,"abstract":"<p><p>Depression affects millions globally, prompting the search for novel treatments. Natural compounds like spice oleoresins show promise due to their bioactive constituents. This study explores the use of Hydroxypropyl-beta-cyclodextrin (HPBCD) for nano-encapsulation to enhance the efficacy of pepper, turmeric, and chilli oleoresins in alleviating depression in a mice model. Chronic unpredictable mild stress (CUMS) was induced for 28 days, followed by administering nano-encapsulated oleoresins (25 mg/kg). Behavioural analyses revealed improved activity, while neurochemical studies showed increased serotonin and dopamine levels with reduced monoamine oxidase (MAO) activity. Western blot highlighted changes in BDNF, supported by histopathological evidence of neuroprotection. Biochemical assays indicated reduced oxidative stress, acetylcholinesterase activity, and enhanced catalase and superoxide dismutase levels. 16S rRNA sequencing revealed improved gut microbiota, with increased beneficial bacteria. Notably, nano-encapsulated chilli oleoresin exhibited the highest efficacy. These findings support the multi-targeted potential of nano-encapsulated spice oleoresins as complementary treatments for depression, addressing neurobiological and gut-related factors.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1-17"},"PeriodicalIF":3.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1080/1028415X.2025.2576621
Haya Majid, Sajad Ul Islam, Sunil Kohli, Nidhi
Background: Branched chain amino acids (BCAA) are essential amino acids that include leucine, isoleucine, and valine. Recent studies indicate that BCAAs might influence cognitive health. This systematic review aims to examine the impact of BCAAs on cognitive function.
Method: The PRISMA guidelines were adhered to, and a literature search of electronic databases was conducted to gather studies meeting the inclusion criteria up to April 2024. Studies that administered BCAA and evaluated cognitive function in patients or healthy participants were included. The risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and the Newcastle-Ottawa Scale for observational studies.
Results: Out of 41 screened studies, 8 met the inclusion criteria, including 353 participants. Risk of bias assessment rated 6 studies as high quality and 2 as medium quality. Analysis showed that 5 studies found no significant changes in cognitive function after BCAA administration, while 3 reported improvements.
Conclusion: BCAA supplementation for cognitive health is influenced by dosage, duration, and underlying health conditions. Some studies suggest potential detrimental effects, while others find no significant impact. Larger, rigorously designed clinical trials are needed to establish clearer causal relationships and optimize therapeutic strategies.
Highlights: BCAAs exert their effects on neuronal signalling, synaptic plasticity, and neurotransmitter regulation, amongst their pharmacological profile in modulating cognitive health.Studying the effects of BCAA administration on cognitive function enables the optimization of therapeutic interventions for cognitive disorders.Investigating the effects of BCAA administration on cognitive function facilitates the identification of biomarkers for monitoring treatment response and disease progression.
{"title":"Efficacy of branched chain amino acid administration on cognitive function: a systematic review.","authors":"Haya Majid, Sajad Ul Islam, Sunil Kohli, Nidhi","doi":"10.1080/1028415X.2025.2576621","DOIUrl":"https://doi.org/10.1080/1028415X.2025.2576621","url":null,"abstract":"<p><strong>Background: </strong>Branched chain amino acids (BCAA) are essential amino acids that include leucine, isoleucine, and valine. Recent studies indicate that BCAAs might influence cognitive health. This systematic review aims to examine the impact of BCAAs on cognitive function.</p><p><strong>Method: </strong>The PRISMA guidelines were adhered to, and a literature search of electronic databases was conducted to gather studies meeting the inclusion criteria up to April 2024. Studies that administered BCAA and evaluated cognitive function in patients or healthy participants were included. The risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and the Newcastle-Ottawa Scale for observational studies.</p><p><strong>Results: </strong>Out of 41 screened studies, 8 met the inclusion criteria, including 353 participants. Risk of bias assessment rated 6 studies as high quality and 2 as medium quality. Analysis showed that 5 studies found no significant changes in cognitive function after BCAA administration, while 3 reported improvements.</p><p><strong>Conclusion: </strong>BCAA supplementation for cognitive health is influenced by dosage, duration, and underlying health conditions. Some studies suggest potential detrimental effects, while others find no significant impact. Larger, rigorously designed clinical trials are needed to establish clearer causal relationships and optimize therapeutic strategies.</p><p><strong>Highlights: </strong>BCAAs exert their effects on neuronal signalling, synaptic plasticity, and neurotransmitter regulation, amongst their pharmacological profile in modulating cognitive health.Studying the effects of BCAA administration on cognitive function enables the optimization of therapeutic interventions for cognitive disorders.Investigating the effects of BCAA administration on cognitive function facilitates the identification of biomarkers for monitoring treatment response and disease progression.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1-16"},"PeriodicalIF":3.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1080/1028415X.2025.2583391
Paulo M A Lima, Beatriz A Lima, Gleisy K N Gonçalves, Daniela R C Fóscolo, Juliana B Guimarães, Helton O Campos, Cândido C Coimbra
Objective: The endocannabinoid system (ECS) plays a pivotal role in regulating energy balance. While ECS activation stimulates appetite and increases preference for palatable food, it also enhances energy expenditure by motivating physical activity. This study investigated the impact of two key energy balance modulators - consumption of a palatable diet and the practice of aerobic physical activity - on the expression of CB1 receptor and NAPE-PLD enzyme in the rat brain.
Methods: Male Wistar rats, weaned at 3 weeks, were divided into 4 groups: standard-diet untrained, standard-diet trained, palatable-diet untrained, and palatable-diet trained. Trained groups underwent treadmill exercise while the palatable diet groups were fed accordingly. After 8 weeks, rats were euthanized for blood and brain collection. Western blotting assessed CB1 and NAPE-PLD proteins expression in the frontal cortex, hypothalamus, and preoptic area. Physical performance, body weight, adiposity index, and plasma levels of leptin, insulin, and glucose were measured.
Results: Aerobic training enhanced physical performance, while a palatable diet increased the adiposity index and plasma leptin levels. In the hypothalamus, both interventions reduced CB1 and NAPE-PLD proteins, while increasing them in the frontal cortex. Physical training and the palatable diet decreased NAPE-PLD in the preoptic area.
Discussion: These findings indicate that exposure to a palatable diet and aerobic training during early life exerts distinct effects on ECS signaling within the central nervous system. This study provides novel evidence that dietary and physical activity patterns can differentially shape brain ECS components, offering insights into their potential roles in energy homeostasis and obesity development.
{"title":"Effect of physical training and palatable diet consumption on the expression of endocannabinoid system components in the rat brain.","authors":"Paulo M A Lima, Beatriz A Lima, Gleisy K N Gonçalves, Daniela R C Fóscolo, Juliana B Guimarães, Helton O Campos, Cândido C Coimbra","doi":"10.1080/1028415X.2025.2583391","DOIUrl":"10.1080/1028415X.2025.2583391","url":null,"abstract":"<p><strong>Objective: </strong>The endocannabinoid system (ECS) plays a pivotal role in regulating energy balance. While ECS activation stimulates appetite and increases preference for palatable food, it also enhances energy expenditure by motivating physical activity. This study investigated the impact of two key energy balance modulators - consumption of a palatable diet and the practice of aerobic physical activity - on the expression of CB1 receptor and NAPE-PLD enzyme in the rat brain.</p><p><strong>Methods: </strong>Male Wistar rats, weaned at 3 weeks, were divided into 4 groups: standard-diet untrained, standard-diet trained, palatable-diet untrained, and palatable-diet trained. Trained groups underwent treadmill exercise while the palatable diet groups were fed accordingly. After 8 weeks, rats were euthanized for blood and brain collection. Western blotting assessed CB1 and NAPE-PLD proteins expression in the frontal cortex, hypothalamus, and preoptic area. Physical performance, body weight, adiposity index, and plasma levels of leptin, insulin, and glucose were measured.</p><p><strong>Results: </strong>Aerobic training enhanced physical performance, while a palatable diet increased the adiposity index and plasma leptin levels. In the hypothalamus, both interventions reduced CB1 and NAPE-PLD proteins, while increasing them in the frontal cortex. Physical training and the palatable diet decreased NAPE-PLD in the preoptic area.</p><p><strong>Discussion: </strong>These findings indicate that exposure to a palatable diet and aerobic training during early life exerts distinct effects on ECS signaling within the central nervous system. This study provides novel evidence that dietary and physical activity patterns can differentially shape brain ECS components, offering insights into their potential roles in energy homeostasis and obesity development.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-06-02DOI: 10.1080/1028415X.2025.2509750
Tejinder Kaur, Varinder Singh, Richa Shri
Carica papaya is a popular fruit valued for its nutritive and diverse medicinal activities. Traditionally, it is used for its varied effects, including those on the central nervous system. The present study investigated the effect of hydroethanolic extract and diet enriched with papaya fruit on depression-like behavior in mice. The extract was standardized with respect to total phenolics, total carbohydrate and total protein contents. The antidepressant effects of the extract and enriched diet (standard diet augmented with 5% w/w papaya pulp powder) were evaluated using the forced swim test (FST) and tail suspension test (TST) in mice. The effect of diet on physiological parameters of the mice was also studied to determine any adverse effects. The extract was found to contain appreciable levels of phenols, carbohydrates and proteins. The extract showed dose-dependent antidepressant activity, as evident by a decrease in the immobility time in the FST and TST. Pre-treatment with the test diet for one month also produced significant antidepressant-like and a reduction in body weight in animals. The results revealed significant antidepressant activity of Carica papaya fruit extract and diet in mice. Since diet is a keystone for well-being, the incorporation of papaya in the diet, after detailed investigation, may prove beneficial in the prevention of depression.
{"title":"Antidepressant potential of <i>Carica Papaya</i> fruit extract and diet: behavioral and physiological effects in mice models.","authors":"Tejinder Kaur, Varinder Singh, Richa Shri","doi":"10.1080/1028415X.2025.2509750","DOIUrl":"10.1080/1028415X.2025.2509750","url":null,"abstract":"<p><p><i>Carica papaya</i> is a popular fruit valued for its nutritive and diverse medicinal activities. Traditionally, it is used for its varied effects, including those on the central nervous system. The present study investigated the effect of hydroethanolic extract and diet enriched with papaya fruit on depression-like behavior in mice. The extract was standardized with respect to total phenolics, total carbohydrate and total protein contents. The antidepressant effects of the extract and enriched diet (standard diet augmented with 5% w/w papaya pulp powder) were evaluated using the forced swim test (FST) and tail suspension test (TST) in mice. The effect of diet on physiological parameters of the mice was also studied to determine any adverse effects. The extract was found to contain appreciable levels of phenols, carbohydrates and proteins. The extract showed dose-dependent antidepressant activity, as evident by a decrease in the immobility time in the FST and TST. Pre-treatment with the test diet for one month also produced significant antidepressant-like and a reduction in body weight in animals. The results revealed significant antidepressant activity of <i>Carica papaya</i> fruit extract and diet in mice. Since diet is a keystone for well-being, the incorporation of papaya in the diet, after detailed investigation, may prove beneficial in the prevention of depression.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1334-1341"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-05-28DOI: 10.1080/1028415X.2025.2509751
Sundus S Lateef, Vanessa L Mueller, Eloisa Vendematti, Vagner A Benedito, Joseph C Gigliotti, R Chris Skinner, Janet C Tou
Objective: To investigate the impact of drinking different caloric sweeteners from immaturity to young adulthood on hypothalamic controlled physiological functions and hypothalamic global gene expression using a rat model.
Methods: Young female Sprague-Dawley rats (age 28 days) were randomly assigned (n = 7 rats/group) to drink water sweetened with 13% (w/w) sugar as either high fructose corn syrup (HFCS), sucrose, fructose, or water (control) for 8 weeks. Hypothalamic controlled physiological function measurements included: energy intake, stress, and estrous cycles. RNA-sequencing (RNA-Seq) was used to investigate global differentially expressed genes (DEGs) in the hypothalamus.
Results: Rats drinking HFCS and sucrose solution increased liquid intake, but reduced food intake. Rats drinking HFCS had the highest (p < 0.05) absolute adrenal weight, which is indicative of chronic stress, and had lengthened estrous cycles. The DEGs with the highest fold changes in the hypothalamus of rats drinking HFCS compared to sucrose and fructose were involved in circadian sleep cycles, neuronal processes, and Engrailed-2 (En2) identified in autism spectrum disorder (ASD).
Conclusion: Among the different caloric-sweetened solutions, young female rats drinking HFCS solution showed food selectivity, elevated basal stress, and reproductive irregularity, which are characteristics associated with ASD. RNA-Seq revealed DEGs in rats drinking HFCS solution, included disrupted circadian sleep cycles, neurotoxicity, and ASD. The results of this preclinical study suggest that HFCS intake should be limited due to its potential for increasing the risk of neurodevelopmental disorders.
{"title":"Hypothalamic regulated physiological function and gene expression changes suggest high fructose corn syrup intake affects neurodevelopment in adolescent female rats.","authors":"Sundus S Lateef, Vanessa L Mueller, Eloisa Vendematti, Vagner A Benedito, Joseph C Gigliotti, R Chris Skinner, Janet C Tou","doi":"10.1080/1028415X.2025.2509751","DOIUrl":"10.1080/1028415X.2025.2509751","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the impact of drinking different caloric sweeteners from immaturity to young adulthood on hypothalamic controlled physiological functions and hypothalamic global gene expression using a rat model.</p><p><strong>Methods: </strong>Young female Sprague-Dawley rats (age 28 days) were randomly assigned (<i>n</i> = 7 rats/group) to drink water sweetened with 13% (w/w) sugar as either high fructose corn syrup (HFCS), sucrose, fructose, or water (control) for 8 weeks. Hypothalamic controlled physiological function measurements included: energy intake, stress, and estrous cycles. RNA-sequencing (RNA-Seq) was used to investigate global differentially expressed genes (DEGs) in the hypothalamus.</p><p><strong>Results: </strong>Rats drinking HFCS and sucrose solution increased liquid intake, but reduced food intake<i>.</i> Rats drinking HFCS had the highest (<i>p</i> < 0.05) absolute adrenal weight, which is indicative of chronic stress, and had lengthened estrous cycles. The DEGs with the highest fold changes in the hypothalamus of rats drinking HFCS compared to sucrose and fructose were involved in circadian sleep cycles, neuronal processes, and <i>Engrailed-2 (En2)</i> identified in autism spectrum disorder (ASD).</p><p><strong>Conclusion: </strong>Among the different caloric-sweetened solutions, young female rats drinking HFCS solution showed food selectivity, elevated basal stress, and reproductive irregularity, which are characteristics associated with ASD. RNA-Seq revealed DEGs in rats drinking HFCS solution, included disrupted circadian sleep cycles, neurotoxicity, and ASD. The results of this preclinical study suggest that HFCS intake should be limited due to its potential for increasing the risk of neurodevelopmental disorders.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1342-1359"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-05-26DOI: 10.1080/1028415X.2025.2509753
Amanda N Carey, Derek R Fisher, Danielle S Cahoon, Barbara Shukitt-Hale
Objectives: Chronic microglial activation drives neuroinflammation, contributing to neurodegenerative diseases and cognitive decline. Walnuts and blueberries (BB) have been demonstrated to reduce neuroinflammation, but it is unknown whether they act synergistically to enhance the effects seen with individual treatment. This study examined the individual and synergistic effects of walnut oil (WO) and BB on lipopolysaccharide (LPS)-induced neuroinflammation in rat microglial cells. The effects of pretreatment duration and concentration were also explored.
Methods: Rat microglial cells were pretreated for 48 hours, one, two, or four weeks with 0.05, 0.1, 0.2, 0.5 and 1.0 mg/mL BB extract, WO or WOBB, followed by exposure to LPS (100 ng/mL). Cell viability was assessed and standard immunochemical techniques were used to measure levels of the inflammatory biomarkers: nitrite, inducible nitrous oxide synthase (iNOS), and cyclooxygenase-2 (COX-2).
Results: BB, WO, and WOBB reduced LPS-induced nitrite, COX-2 and iNOS relative to control, with higher concentrations and longer treatment durations typically being most beneficial. All treatments showed similar ability to reduce iNOS expression, while BB had a stronger effect on reducing nitrite production than WO and WOBB. There were no significant differences between treatment effects on COX-2 expression.
Conclusion: BB and WO each reduced LPS-induced inflammation in microglia, but their combination was not more effective, suggesting no synergistic effect. This result suggests that they may work through similar mechanisms to attenuate inflammation in microglia. Overall, the reduction in neuroinflammation shows that the addition of BBs or walnuts to the diet may attenuate neuroinflammation linked to neurodegeneration.
{"title":"Individual and combined walnut oil and blueberry attenuate lipopolysaccharide-induced neuroinflammation in rat microglia.","authors":"Amanda N Carey, Derek R Fisher, Danielle S Cahoon, Barbara Shukitt-Hale","doi":"10.1080/1028415X.2025.2509753","DOIUrl":"10.1080/1028415X.2025.2509753","url":null,"abstract":"<p><strong>Objectives: </strong>Chronic microglial activation drives neuroinflammation, contributing to neurodegenerative diseases and cognitive decline. Walnuts and blueberries (BB) have been demonstrated to reduce neuroinflammation, but it is unknown whether they act synergistically to enhance the effects seen with individual treatment. This study examined the individual and synergistic effects of walnut oil (WO) and BB on lipopolysaccharide (LPS)-induced neuroinflammation in rat microglial cells. The effects of pretreatment duration and concentration were also explored.</p><p><strong>Methods: </strong>Rat microglial cells were pretreated for 48 hours, one, two, or four weeks with 0.05, 0.1, 0.2, 0.5 and 1.0 mg/mL BB extract, WO or WOBB, followed by exposure to LPS (100 ng/mL). Cell viability was assessed and standard immunochemical techniques were used to measure levels of the inflammatory biomarkers: nitrite, inducible nitrous oxide synthase (iNOS), and cyclooxygenase-2 (COX-2).</p><p><strong>Results: </strong>BB, WO, and WOBB reduced LPS-induced nitrite, COX-2 and iNOS relative to control, with higher concentrations and longer treatment durations typically being most beneficial. All treatments showed similar ability to reduce iNOS expression, while BB had a stronger effect on reducing nitrite production than WO and WOBB. There were no significant differences between treatment effects on COX-2 expression.</p><p><strong>Conclusion: </strong>BB and WO each reduced LPS-induced inflammation in microglia, but their combination was not more effective, suggesting no synergistic effect. This result suggests that they may work through similar mechanisms to attenuate inflammation in microglia. Overall, the reduction in neuroinflammation shows that the addition of BBs or walnuts to the diet may attenuate neuroinflammation linked to neurodegeneration.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1360-1371"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Alzheimer's disease (AD) and Multiple sclerosis (MS) are progressive neurodegenerative conditions. AD is characterized by neuroinflammation, plaques, tangles, and synaptic loss, while MS involves inflammatory demyelination. Although AD and MS have different pathogenesis, they may share some neurodegenerative mechanisms, so similar therapeutic strategies could potentially be effective for both. Research suggests that natural substances such as carotenoids may be beneficial for neurological disorders. Notably, Astaxanthin (AXT) has demonstrated promising effects as an adjunct therapy.
Methods: In this review, we aimed to shed light on the effects of AXT on MS and AD by searching published articles from inception to 1 August 2024, in the Scopus, Google Scholar, PubMed, and PubMed/Medline databases.
Results: The therapeutic effects of AXT in neurodegenerative disorders are associated with its antioxidant, anti-inflammatory, anti-apoptotic, and neuroplasticity improvement properties. Literature have confirmed that AXT can positively impact AD by modulating anti-inflammatory and pro-inflammatory cytokines, mitochondrial function, amyloid beta production, and microglial activation, which collectively leads to memory and learning enhancement. Additionally, AXT has demonstrated advantages in MS by reducing demyelination and preserving nerve functions through its effects on pro- and anti-inflammatory cytokines, as well as promoting the differentiation of oligodendrocyte precursors into mature oligodendrocytes.
Conclusion: AXT, as a promising versatile adjunctive neuroprotective therapy, can influence multiple recovery pathways rather than focusing on a single target or mechanism. According to the results of preclinical studies, we can recommend assessing AXT effects in clinical trials of AD and MS.
{"title":"Astaxanthin as an adjunct therapy in Alzheimer's disease and multiple sclerosis: neuroprotective mechanisms and future perspective.","authors":"Farzane Rezaei Yazdi, Fatemeh Taghizadeh, Soraya Parvari, Parinaz Javanbakht, Sina Mojaverrostami, Davood Zarini, Iraj Ragerdi Kashani","doi":"10.1080/1028415X.2025.2516620","DOIUrl":"10.1080/1028415X.2025.2516620","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) and Multiple sclerosis (MS) are progressive neurodegenerative conditions. AD is characterized by neuroinflammation, plaques, tangles, and synaptic loss, while MS involves inflammatory demyelination. Although AD and MS have different pathogenesis, they may share some neurodegenerative mechanisms, so similar therapeutic strategies could potentially be effective for both. Research suggests that natural substances such as carotenoids may be beneficial for neurological disorders. Notably, Astaxanthin (AXT) has demonstrated promising effects as an adjunct therapy.</p><p><strong>Methods: </strong>In this review, we aimed to shed light on the effects of AXT on MS and AD by searching published articles from inception to 1 August 2024, in the Scopus, Google Scholar, PubMed, and PubMed/Medline databases.</p><p><strong>Results: </strong>The therapeutic effects of AXT in neurodegenerative disorders are associated with its antioxidant, anti-inflammatory, anti-apoptotic, and neuroplasticity improvement properties. Literature have confirmed that AXT can positively impact AD by modulating anti-inflammatory and pro-inflammatory cytokines, mitochondrial function, amyloid beta production, and microglial activation, which collectively leads to memory and learning enhancement. Additionally, AXT has demonstrated advantages in MS by reducing demyelination and preserving nerve functions through its effects on pro- and anti-inflammatory cytokines, as well as promoting the differentiation of oligodendrocyte precursors into mature oligodendrocytes.</p><p><strong>Conclusion: </strong>AXT, as a promising versatile adjunctive neuroprotective therapy, can influence multiple recovery pathways rather than focusing on a single target or mechanism. According to the results of preclinical studies, we can recommend assessing AXT effects in clinical trials of AD and MS.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1399-1423"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-06-10DOI: 10.1080/1028415X.2025.2514490
Jenneffer Rayane Braga Tibaes, Gabriela Barbosa Fagundes, Lais Bhering Martins, Ana Maria Dos Santos Rodrigues, Alexandre Camargo Campos, Leticia Maria de Souza Cordeiro, Antonio Lucio Teixeira, Adaliene Versiani Matos Ferreira
Objective: Comparison of the effect of acute daytime fasting on mood, satiety, and neurotrophic factors in females with (OB) and without obesity (N-OB).
Methods: Non-randomized single-arm feasibility trial. Data were collected at an outpatient clinic and from real-world settings. Participants were evaluated after 10 h of nocturnal fasting (T1) and following a 10-hour diurnal fasting period (T2) after consuming a standardized breakfast. Mood, subjective feelings of satiety, food cravings, and neurotrophic factors brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) were assessed.
Results: Fifty-four participants were enrolled in the study [mean age 31 (SD 9)]. One participant from the OB group dropped out before T2, leaving 53 participants (N-OB: n = 29, OB: n = 24). Both groups experienced increased hunger and decreased satiety and fullness after T2. Females with obesity had a greater increase in hunger (p = 0.02). Depression and anger symptoms increased in the OB group, whereas fatigue increased in the N-OB group after T2. NGF increased slightly in the N-OB group after T2, while BDNF and GDNF remained unchanged.
Conclusion: Daytime fasting during daily activities affects mood and eating behavior, especially in females with obesity. Fasting interventions should be tailored to individual needs, considering these differential effects.
目的:比较急性日间禁食对有(OB)和无(N-OB)肥胖女性的情绪、饱腹感和神经营养因子的影响。方法:非随机单组可行性试验。数据收集于门诊诊所和现实世界。参与者在夜间禁食10小时(T1)和食用标准化早餐后10小时的日间禁食期(T2)后进行评估。评估情绪、主观饱腹感、食物渴望和神经营养因子脑源性神经营养因子(BDNF)、神经生长因子(NGF)和胶质细胞系源性神经营养因子(GDNF)。结果:54名受试者入组[平均年龄31岁(SD 9)]。1名OB组参与者在T2前退出,剩下53名参与者(n -OB: n = 29, OB: n = 24)。两组在T2后都经历了饥饿感的增加和饱腹感的减少。肥胖女性的饥饿感增加更大(p = 0.02)。T2后OB组抑郁和愤怒症状加重,而N-OB组疲劳症状加重。T2后N-OB组NGF略有增加,而BDNF和GDNF保持不变。结论:在日常活动中白天禁食会影响情绪和饮食行为,尤其是肥胖女性。考虑到这些不同的影响,禁食干预措施应根据个人需要量身定制。试验注册:ClinicalTrials.gov标识符:NCT03532672。
{"title":"Effects of a single 10-hour daytime fasting intervention on mood and appetite in female adults with and without obesity: a real-world feasibility trial.","authors":"Jenneffer Rayane Braga Tibaes, Gabriela Barbosa Fagundes, Lais Bhering Martins, Ana Maria Dos Santos Rodrigues, Alexandre Camargo Campos, Leticia Maria de Souza Cordeiro, Antonio Lucio Teixeira, Adaliene Versiani Matos Ferreira","doi":"10.1080/1028415X.2025.2514490","DOIUrl":"10.1080/1028415X.2025.2514490","url":null,"abstract":"<p><strong>Objective: </strong>Comparison of the effect of acute daytime fasting on mood, satiety, and neurotrophic factors in females with (OB) and without obesity (N-OB).</p><p><strong>Methods: </strong>Non-randomized single-arm feasibility trial. Data were collected at an outpatient clinic and from real-world settings. Participants were evaluated after 10 h of nocturnal fasting (T1) and following a 10-hour diurnal fasting period (T2) after consuming a standardized breakfast. Mood, subjective feelings of satiety, food cravings, and neurotrophic factors brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) were assessed.</p><p><strong>Results: </strong>Fifty-four participants were enrolled in the study [mean age 31 (SD 9)]. One participant from the OB group dropped out before T2, leaving 53 participants (N-OB: n = 29, OB: n = 24). Both groups experienced increased hunger and decreased satiety and fullness after T2. Females with obesity had a greater increase in hunger (<i>p</i> = 0.02). Depression and anger symptoms increased in the OB group, whereas fatigue increased in the N-OB group after T2. NGF increased slightly in the N-OB group after T2, while BDNF and GDNF remained unchanged.</p><p><strong>Conclusion: </strong>Daytime fasting during daily activities affects mood and eating behavior, especially in females with obesity. Fasting interventions should be tailored to individual needs, considering these differential effects.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03532672.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1372-1385"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-06-15DOI: 10.1080/1028415X.2025.2516627
Fernanda Nunes Maia, Bruna Yhang da Costa Silva, Renan Souto Pereira, Larissa da Silva Albuquerque, Vitor Wagner de Sousa Lacerda, José Artur Costa D'Almeida, Maria Luisa Pereira de Melo
Objective: To identify dietary total antioxidant capacity (DTAC) in people with MS (PwMS) and evaluate its interrelation with nutritional status and disease progression.
Methods: Cross-sectional, quantitative study with 127 patients with MS recruited from the Interdisciplinary Center for Assistance, Research and Teaching in Neuroimmunology (CIAPEN) (Fortaleza, Ceará, Brazil). The clinical parameters were clinical phenotype, the expanded disability status scale (EDSS), the medical research council (MRC) muscle scale, and Magnetic Resonance Imaging (MRI) evaluation. Weight and height measurements were obtained to calculate the body mass index (BMI), waist circumference (WC) and estimate body fat percentage (BF%). The DTAC was estimated using food intake data from the 24DR and the intake of antioxidant supplements.
Results: As for the nutritional status, it was found that 48 (37.80%) and 64 (50.39%) had excess adiposity according to the BMI and BF%, respectively, and 67 (53.60%) had elevated WC. Higher DTAC was associated with higher WC (r = 0.192, p = 0.032) and BF% (r = 0.246, p = 0.005); and higher intake of energy (r = 0.418, p < 0.001). There was no association between the clinical phenotype of the disease, the EDSS, the presence of visible lesions and the DTAC tertiles. However, in the unadjusted model, it was observed that the second tertile of DTAC reduced by 64% (OR = 0.36; 95% CI: 0.14-0.96) the individual's chance of having lower muscle strength, assessed by the MRC muscle scale.
Conclusion: Healthy nutrition, especially sufficient intake of dietary antioxidants, should be encouraged in PwMS.
目的:了解多发性硬化症(PwMS)患者膳食总抗氧化能力(DTAC),并评价其与营养状况和疾病进展的关系。方法:从神经免疫学跨学科援助、研究和教学中心(CIAPEN) (Fortaleza, cear,巴西)招募127例MS患者进行横断面定量研究。临床参数包括临床表型、扩展残疾状态量表(EDSS)、医学研究委员会(MRC)肌肉量表和磁共振成像(MRI)评价。测量体重和身高,计算体重指数(BMI)、腰围(WC)和体脂率(BF%)。DTAC是根据24DR的食物摄入数据和抗氧化剂补充剂的摄入来估计的。结果:营养状况方面,BMI和BF%分别为48例(37.80%)和64例(50.39%),WC升高67例(53.60%)。较高的DTAC与较高的WC (r = 0.192, p = 0.032)和BF% (r = 0.246, p = 0.005)相关;结论:PwMS患者应提倡健康营养,特别是膳食中摄入足够的抗氧化剂。
{"title":"Dietary total antioxidant capacity associated with nutritional status and clinical condition of patients with multiple sclerosis.","authors":"Fernanda Nunes Maia, Bruna Yhang da Costa Silva, Renan Souto Pereira, Larissa da Silva Albuquerque, Vitor Wagner de Sousa Lacerda, José Artur Costa D'Almeida, Maria Luisa Pereira de Melo","doi":"10.1080/1028415X.2025.2516627","DOIUrl":"10.1080/1028415X.2025.2516627","url":null,"abstract":"<p><strong>Objective: </strong>To identify dietary total antioxidant capacity (DTAC) in people with MS (PwMS) and evaluate its interrelation with nutritional status and disease progression.</p><p><strong>Methods: </strong>Cross-sectional, quantitative study with 127 patients with MS recruited from the Interdisciplinary Center for Assistance, Research and Teaching in Neuroimmunology (CIAPEN) (Fortaleza, Ceará, Brazil). The clinical parameters were clinical phenotype, the expanded disability status scale (EDSS), the medical research council (MRC) muscle scale, and Magnetic Resonance Imaging (MRI) evaluation. Weight and height measurements were obtained to calculate the body mass index (BMI), waist circumference (WC) and estimate body fat percentage (BF%). The DTAC was estimated using food intake data from the 24DR and the intake of antioxidant supplements.</p><p><strong>Results: </strong>As for the nutritional status, it was found that 48 (37.80%) and 64 (50.39%) had excess adiposity according to the BMI and BF%, respectively, and 67 (53.60%) had elevated WC. Higher DTAC was associated with higher WC (r = 0.192, <i>p</i> = 0.032) and BF% (r = 0.246, <i>p</i> = 0.005); and higher intake of energy (r = 0.418, <i>p</i> < 0.001). There was no association between the clinical phenotype of the disease, the EDSS, the presence of visible lesions and the DTAC tertiles. However, in the unadjusted model, it was observed that the second tertile of DTAC reduced by 64% (OR = 0.36; 95% CI: 0.14-0.96) the individual's chance of having lower muscle strength, assessed by the MRC muscle scale.</p><p><strong>Conclusion: </strong>Healthy nutrition, especially sufficient intake of dietary antioxidants, should be encouraged in PwMS.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1424-1432"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}