Brain Research最新文献

{"title":"Nanoparticle-enhanced delivery of resveratrol for targeted therapy of glioblastoma: Modulating the Akt/GSK-3β/NF-kB pathway in C6 glioma cells.","authors":"Gurpreet Singh, Paras Famta, Saurabh Shah, Ganesh Vambhurkar, Giriraj Pandey, Rahul Kumar, Prakash Kumar, Atul Mourya, Jitender Madan, Saurabh Srivastava, Dharmendra Kumar Khatri","doi":"10.1016/j.brainres.2024.149411","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149411","url":null,"abstract":"<p><strong>Objective: </strong>The study aims to explore Resveratrol (RES) as a potential therapeutic agent for Glioblastoma multiforme (GBM), a challenging brain cancer. RES, a polyphenolic compound with known benefits in various diseases including cancer, has shown promise in inhibiting glioma progression through its effects on the AKT signaling pathways. However, its limited ability to cross the blood-brain barrier restricts its clinical application in GBM treatment. This study seeks to enhance efficacy of RES by developing RES-loaded nanoparticles designed to improve penetration into glioma cells and potentially overcome the blood-brain barrier, thereby enhancing therapeutic outcomes.</p><p><strong>Methods: </strong>Albumin nanoparticles were prepared and characterized using FT-IR, X-RD, and SEM to determine particle size. In vitro experiments were conducted using the C6 glioma cell line, employing MTT assays, Immunofluorescence, DC-FDA staining, and western blot analysis. Molecular docking studies were also performed to assess ability of RES to inhibit the AKT/GSK-3β/NF-kB pathway.</p><p><strong>Results: </strong>In vitro results demonstrated that RES-loaded nanoparticles induced apoptosis and reduced proliferation of C6 glioma cells compared to controls. Molecular docking studies confirmed RES's potential as an inhibitor targeting the AKT/GSK-3β/NF-kB pathway. Western blot analysis revealed downregulation of AKT and GSK-3β expression in cells treated with RES-loaded nanoparticles, accompanied by increased caspase 1 levels and decreased bcl2 expression, indicative of apoptosis.</p><p><strong>Conclusion: </strong>The findings suggest that RES effectively targets the AKT/GSK-3β/NF-kB signaling pathway in glioma cells. Furthermore, RES-loaded albumin nanoparticles significantly enhance therapeutic efficacy by improving cellular penetration, highlighting their potential in advancing GBM treatment strategies.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149411"},"PeriodicalIF":2.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881173","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}

{"title":"Dynamic analysis of frequency specificity in multilayer brain networks.","authors":"Ming Ke, Peihui Cao, Xiaoliang Chai, Xinyi Yao, Guangyao Liu","doi":"10.1016/j.brainres.2024.149418","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149418","url":null,"abstract":"<p><p>The brain is a highly complex and delicate system, and its internal neural processes are manifested as the interweaving and superposition of multi-frequency neural signals. However, traditional brain network studies are often limited to the whole frequency band or a specific frequency band, ignoring the potentially profound impact of the diversity of information within the frequency on the dynamics of brain networks. To comprehensively and deeply analyze this phenomenon, the present study is devoted to exploring the specific performance of brain networks at different frequencies. We used the maximum overlap discrete wavelet transform technique to finely divide the time series data into the following frequency bands: scale 1 (0.125-0.25 Hz), scale 2 (0.06-0.125 Hz), scale 3 (0.03-0.06 Hz) and scale 4 (0.015-0.03 Hz). Based on these frequency bands, we constructed multilayer networks from both dynamic and static perspectives, respectively. From the dynamic perspective, we quantitatively evaluated the dynamic differences among different frequency bands using metrics such as flexibility, promiscuity, integration, and recruitment, and found that scale 3 and scale 4 bands performed particularly well. In contrast, from a static perspective, we measured the cross-frequency interaction capability between different frequency bands through metrics such as multilayer clustering coefficient and entropy of multiplexing degree, and the results show that scale 2, scale 3, and scale 4 band networks have enhanced global integration capability and local capability. In addition, we explored the correlation of gender and age with the properties of brain networks in different frequency bands. In scale 1 frequency bands, the organization of brain functions showed significant gender differences, while in scale 2 frequency bands, there was a significant correlation between age and global efficiency. By integrating the dual perspectives of time and frequency domains, this study not only reveals the critical role of frequency specificity in the brain's information processing and functional organization but also provides new perspectives for understanding the complex working mechanisms of the brain as well as gender- and age-related cognitive differences.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149418"},"PeriodicalIF":2.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881164","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}

{"title":"Titration of cuprizone induces reliable demyelination.","authors":"Nicole Wigger, Johann Krüger, Elise Vankriekelsvenne, Markus Kipp","doi":"10.1016/j.brainres.2024.149410","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149410","url":null,"abstract":"<p><p>Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Cuprizone-induced demyelination, wherein mice are fed a diet containing the copper chelator cuprizone, is a well-established model that replicates key features of demyelination and remyelination. However, the dose-response relationship of cuprizone is complex; high concentrations can induce toxicity, whereas insufficient doses may fail to produce reliable demyelination across subjects. This study aimed to investigate whether titration of the cuprizone concentration results in reliable acute demyelination and weight stabilization. To this end, experimental animals were intoxicated with cuprizone over a period of 5 weeks to induce acute demyelination. In one group, during the first 10 days, the initial cuprizone dose was gradually reduced until the experimental animals showed stable weights. Another group was subjected to a continuous cuprizone intoxication protocol without adaptions. Histological analyses were performed to quantify the extent of demyelination and glia activation. Animals of both groups experienced significant weight loss. Histological analyses revealed, despite adopting the cuprizone concentration, substantial demyelination of various brain regions, including the corpus callosum. This pattern was consistent across multiple staining methods, including anti-proteolipid protein (PLP), anti-myelin basic protein (MBP), and luxol-fast-blue (LFB) stains. Additionally, grey matter regions, specifically the neocortex, demonstrated significant demyelination. Accompanying these changes, there was notable activation and accumulation of microglia and astrocytes in white and grey matter regions. These histopathological changes were comparably pronounced in both cuprizone-treated groups. In summary, we demonstrate that titration of cuprizone is a reliable approach to induce acute demyelination in the mouse forebrain. This work represents a significant step toward refining animal models of MS, contributing to the broader effort of understanding and treating this complex disease.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149410"},"PeriodicalIF":2.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881179","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}

{"title":"Long-term impact of congenital Zika virus infection on the rat hippocampus: Neuroinflammatory, glial alterations and sex-specific effects.","authors":"Adriana Souza Dos Santos, Meirylanne Gomes da Costa, Wellington de Almeida, Gabrielle Batista de Aguiar, Anna Luísa Lothhammer Bohn, Ana Paula Rodrigues Martini, Andrey Vinicios Soares Carvalho, Thiago Ângelo Smaniotto, Alessandra Schmitt Rieder, Ana Paula Muterle Varelad, Thais Fumaco Teixeirad, Paulo Michel Roehe, Angela Terezinha de Souza Wyse, Carla Dalmaz, Carlos Alexandre Netto, Lenir Orlandi Pereira","doi":"10.1016/j.brainres.2024.149421","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149421","url":null,"abstract":"<p><p>Congenital Zika Syndrome (CZS) is a condition that arises when a neonate presents with abnormalities resulting from Zika virus infection during gestation. While microcephaly is a prominent feature of the syndrome, other forms of brain damage are also observed, often accompanied by significant neurological complications. It is therefore essential to investigate the long-term effects of CZS, with special attention to sex differences, particularly concerning hippocampal function, given its vulnerability to viral infections. The aim of this study was to evaluate the long-term impacts on cognitive and memory functions, as well as neuroinflammatory and glial alterations in the hippocampus, in offspring of both sexes exposed to a model of congenital Zika virus infection. Pregnant rats were subcutaneously inoculated with ZIKV-BR at a dose of 1 × 10^7 plaque-forming units (PFU mL^-1) of ZIKV isolated in Brazil (ZIKV-BR) on gestational day 18 (G18). From postnatal day 70, the animals underwent behavioral tests. On postnatal day 80, the animals were euthanized, and hippocampal samples were collected for biochemical and histological analyses. In the open field test, females displayed more exploratory behavior and less grooming, while no significant differences in locomotion were observed between the sexes. Additionally, ZIKV-exposed females showed a reduction in grooming behavior compared to ZIKV-exposed males. In the memory test, males in the ZIKV group exhibited greater memory impairment, spending more time to locate the correct quadrant, while females showed relatively better performance. Neuroinflammatory markers, such as TNF-α, were significantly elevated in the hippocampus of ZIKV-exposed animals, regardless of sex. However, microglial and astrocytic responses, indicated by higher IBA1 and GFAP density, were only observed in male ZIKV rats. In conclusion, our findings suggest that congenital ZIKV exposure leads to sex-specific behavioral and neuroinflammatory alterations. While both males and females exhibited some behavioral changes, males were more significantly impacted in memory performance. Additionally, increased neuroinflammatory markers and glial activation were observed in the hippocampus of ZIKV-exposed animals, with a pronounced response in males. These results highlight the long-term impact of ZIKV infection on neurodevelopment, emphasizing the importance of considering sex differences in studies of congenital ZIKV syndrome.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149421"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876167","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}

{"title":"Asymmetric intra and inter-hemispheric subcellular rat brain correlation of arginyl-aminopeptidase activity during development and aging.","authors":"Manuel Ramírez-Sánchez, Isabel Prieto, Ana Belén Segarra, Inmaculada Banegas, Magdalena Martínez-Cañamero, Germán Domínguez-Vías, Raquel Durán, Francisco Vives","doi":"10.1016/j.brainres.2024.149417","DOIUrl":"10.1016/j.brainres.2024.149417","url":null,"abstract":"<p><p>The functional significance of brain asymmetry is still largely unknown. Studying the level of correlation of neuropeptide-degrading activities between subcellular fractions such as synaptosomal, of the left and right hemispheres of male rats during development and aging could provide relevant data on their functional role during these periods. The present study analyzes the level of correlation of a enkephalin- or angiotensin III-degrading activity, such as membrane-bound arginyl-aminopeptidase activity (M-B ArgAP) between the left versus right homogenate and/or synaptosomal subcellular fractions obtained and processed independently from both brain hemispheres during development and aging. The tested ages were: fetuses, rats of one week, one month, five month and two year old. In homogenate, the results demonstrate high levels of positive correlations (left versus right homogenate) with high levels of significance, without differences among the ages analyzed. In synaptosomes the results demonstrate positive correlations with a level close to statistical significance (left versus right synaptosomes) in fetuses, significant correlations at one week, one month and five months, particularly at one week and five months, and a radical decrease in the level of left versus right correlation between synaptosomes of two-year-old animals, which could suggest a functional loss of the bilateral synaptic interaction that could be carried out at earlier ages by M-B ArgAP activity. The interaction between left or right synaptosomes versus left or right homogenates demonstrate decreasing levels of positive correlation from fetuses to five month old rats, without differences between correlations of the left synaptosomes with correlations of the right ones. However, in two year old rats the values of correlations of the left synaptosomes diverged significantly from the right ones. While left synaptosomal correlations exhibited positive values, the right correlations exhibited negative ones, showing. a clear asymmetry between both sides in aged rats suggesting a marked reduction with aging of the synaptic function in the right hemisphere.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149417"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876119","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}

{"title":"Inhibition of autophagy attenuates cognitive decline and mitochondrial dysfunction in an Alzheimer's disease mouse model with chronic cerebral hypoperfusion.","authors":"Qin Yang, Tingting Chen, Shaofa Li, Chengmin Yang, Xingwu Zheng, Sanying Mao, Ning Liu, Shenglong Mo, Dengxing Li, Meiling Yang, Zhicheng Lu, Lina Tang, Xiaorui Huang, Xia Liu, Chongdong Jian, Yixia Yin, Jingwei Shang","doi":"10.1016/j.brainres.2024.149416","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149416","url":null,"abstract":"<p><p>This study aimed to investigate the impact of chronic cerebral hypoperfusion (CCH) on cognitive function, amyloid-β (Aβ) deposition, cellular autophagy, and mitochondrial dynamics in an Alzheimer's disease (AD) mouse model, and to evaluate the intervention effects of autophagy modulation on these outcomes. Utilizing the APP/PS1 mouse model combined with CCH, we assessed cognitive function, Aβ deposition, and the expression levels of relevant proteins through behavioral tests and immunohistochemical analysis. Our findings revealed pronounced cognitive deficits and increased Aβ deposition in the AD + CCH group mice, along with upregulation of mitochondrial fission proteins (Drp1, Fis1) and downregulation of mitochondrial fusion proteins (Opa1, Mfn1), indicating a shift towards mitochondrial fission and promoting cell apoptosis. Additionally, alterations were observed in the expression levels of cellular autophagy-related proteins (LC3-II, P62), which were reversed by treatment with autophagic inhibitor 3-methyladenine (3-MA). Furthermore, the expression of mitochondrial autophagy-related proteins PINK1 and Parkin was affected, with 3-MA alleviating this effect. In summary, our study elucidates the complex interplay among cognitive decline, increased Aβ deposition, and mitochondrial dysfunction in the AD + CCH model, and suggests that modulating autophagy could be a potential therapeutic strategy for treating the AD + CCH model.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149416"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876125","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}

{"title":"Kynurenine pathway dysregulation as a mechanistic link between cognitive impairment and brain damage: Implications for multiple sclerosis.","authors":"Marie Kupjetz, Tiffany Y Wences Chirino, Niklas Joisten, Philipp Zimmer","doi":"10.1016/j.brainres.2024.149415","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149415","url":null,"abstract":"<p><p>Cognitive impairment is a core symptom of multiple sclerosis (MS), resulting from inflammation-related brain damage and brain network dysfunction. Inflammation also causes dysregulation of the kynurenine pathway which is the primary route of tryptophan catabolism. Kynurenine pathway dysregulation is characterised by a shift in concentrations of tryptophan catabolites, also referred to as kynurenines. Some kynurenines have neurotoxic effects that partly resemble the molecular mechanisms of MS pathophysiology underpinning brain damage and network dysfunction. The kynurenine pathway may therefore qualify as a mechanistic link between systemic inflammation, brain damage, and cognitive impairment in MS. This perspective article (1) provides an overview of inflammation-related KP dysregulation and MS-relevant neuroimmune properties of kynurenines and (2) summarises the current evidence on associations between systemic kynurenines, imaging metrics of brain structure or related markers, and cognitive performance in populations that present with kynurenine pathway dysregulation and are prone to cognitive impairment. These findings (3) are used to set a research agenda for future studies aimed at clarifying the role of the kynurenine pathway in brain damage and cognitive impairment in MS.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149415"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876162","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}

{"title":"Cannabidiol induces autophagy via CB₁ receptor and reduces α-synuclein cytosolic levels.","authors":"Adolfo G Erustes, Vanessa C Abílio, Claudia Bincoletto, Mauro Piacentini, Gustavo J S Pereira, Soraya S Smaili","doi":"10.1016/j.brainres.2024.149414","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149414","url":null,"abstract":"<p><p>Numerous studies have explored the role of cannabinoids in neurological conditions, chronic pain and neurodegenerative diseases. Restoring autophagy has been proposed as a potential target for the treatment of neurodegenerative diseases. In our study, we used a neuroblastoma cell line that overexpresses wild-type α-synuclein to investigate the effects of cannabidiol on autophagy modulation and reduction in the level of cytosolic α-synuclein. Our results demonstrated that cannabidiol enhances the accumulation of LC3-II- and GFP-LC3-positive vesicles, which indicates an increase in autophagic flux. In addition, cannabidiol-treated cells showed a reduction in cytosolic α-synuclein levels. These effects were inhibited when the cells were treated with a CB₁ receptor-selective antagonist, which indicates that the biological effects of cannabidiol are mediated via its interaction with CB₁ receptor. Additionally, we also observed that cannabinoid compounds induce autophagy and α-synuclein degradation after they interact with the CB₁ receptor. In summary, our data suggest that cannabidiol induces autophagy and reduces cytosolic α-synuclein levels. These biological effects are mediated preferentially through the interaction of cannabidiol with CB₁ receptors, and therefore, cannabinoid compounds that act selectively on this receptor could represent a new approach for autophagy modulation and degradation of protein aggregates.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149414"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876121","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}

{"title":"Theta-Gamma Decoupling - A neurophysiological marker of impaired reward processing in Parkinson's disease.","authors":"Rashi Sharma, Nivethida Thirugnanasambandam","doi":"10.1016/j.brainres.2024.149406","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149406","url":null,"abstract":"<p><p>Individuals with Parkinson's disease (PD) exhibit altered reward processing, reflected by a decreased amplitude of an event-related potential (ERP) marker called reward positivity (RewP). Most studies have used RewP to investigate reward behavior due to the high temporal resolution of EEG and its high sensitivity. However, traditional single-electrode ERP analyses often overlook the intricate dynamics of non-phase-locked oscillatory activity and the complex interactions within these neural oscillatory patterns. Studying oscillatory activity is crucial as it provides mechanistic insights into the functional, spatial, and temporal aspects of neuronal processing. To address this gap, we employed a data-driven approach to identify EEG-based markers associated with PD reward processing deficits. Using an openly available 64-channel EEG dataset of 28 age- and sex-matched PD and control participants during a reinforcement learning task, we conducted a comprehensive secondary analysis. First, we employed a cluster-based permutation method to extract ERP markers, finding a consistent decrease in reward positivity in PD, regardless of medication status. Additionally, through region of interest (ROI) analysis on time-frequency data, we identified specific oscillatory patterns during reward processing. PD patients exhibited attenuated theta power and increased gamma power compared to healthy controls (HC). Notably, within the PD group, those off medication showed anterior localization of high gamma power, while those on medication displayed higher posterior gamma power. Building upon these findings, we explored phase-amplitude coupling between theta phase and gamma amplitude measured by the modulation index. We observed a trend of decreased theta-gamma coupling in PD patients, with statistically significant differences between on and off medication conditions. These results highlight the potential role of theta-gamma coupling as a neuromodulatory target for improving goal-oriented behavior in PD. Our correlation analyses suggest that high gamma power is linked to longer disease duration, while reduced reward positivity and low theta-gamma coupling may serve as markers of the dopaminergic impact on reward processing. Thus, our study unveils the intricate time-frequency dynamics underlying reward processing deficits in PD, emphasizing the utility of a data-driven approach to elucidate neural mechanisms and to identify potential therapeutic targets.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149406"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871254","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}

{"title":"Effect of electroacupuncture on metabolic alterations in the hippocampus and dorsal raphe nucleus of Wistar Kyoto rats.","authors":"Xiaoling Zeng, Xuan Yin, Kaiyu Cui, Wenqing Xu, Xiang Li, Wei Zhang, Wei Li, Shifen Xu","doi":"10.1016/j.brainres.2024.149409","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149409","url":null,"abstract":"<p><p>Depression is underpinned by a complex pathogenesis that involves the hippocampus and dorsal raphe nucleus (DRN) of the central nervous system. Although electroacupuncture (EA) is proven to be safe and effective for alleviating depression symptoms and causes minimal side effects its underlying therapeutic mechanism remains unclear. In this study, we performed targeted metabolomics to identify metabolite alterations in the hippocampus and DRN of Wistar Kyoto (WKY) rats and elucidate the role and potential mechanism of action of EA. Our results indicated that 3 weeks of consecutive EA significantly ameliorated depression-like behavior in WKY rats. Targeted metabolomics revealed 42 differentially expressed metabolites (DEMs) in the hippocampus and 97 DEMs in the DRN between Wistar and WKY rats. In addition, we observed 19 hippocampal DEMs and 41 DRN DEMs between WKY and EA-treated rats. Subsequent pathway analyses indicated that these DEMs were primarily enriched in amino acid-related metabolic pathways. Moreover, six DEMs were found to be significantly associated with at least one depression-like behavior, indicating their involvement in the pathogenesis of depression. EA intervention modulated the levels of 1-methylhistidine, 3-methylhistidine, carnosine, and riboflavin in depressed rats. Collectively, these findings demonstrate that disturbances in cerebral metabolites, especially amino acids, may be one of the causes underlying depression in WKY rats, and the therapeutic effect of EA is potentially mediated through the modulation of the levels of these metabolites.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149409"},"PeriodicalIF":2.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870823","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}