Metabolic brain disease最新文献

{"title":"Pharmacologically activating BDNF/TrkB signaling exerted rapid-acting antidepressant-like effects through improving synaptic plasticity and neuroinflammation.","authors":"Si-Rui Sun, Jia-Ning Zhao, Peng-Wei Bi, Hui-Ying Zhang, Guang-Xiang Li, Jiao-Zhao Yan, Yun-Feng Li, Yong-Yu Yin, Hao Cheng","doi":"10.1007/s11011-025-01583-0","DOIUrl":"https://doi.org/10.1007/s11011-025-01583-0","url":null,"abstract":"<p><p>BDNF (Brain-derived neurotrophic factor)/TrkB (tropomyosin receptor kinase B) signaling has great therapeutic potential for depression, but the underlying mechanism remains unclear. This study aims to investigate the molecular mechanism underlying the BDNF/TrkB signaling-mediated antidepressant effects. Chronic Cort drinking for 4 weeks and a single injection of LPS for 24 h were used to induce depression-like behaviors; this study used 7,8-dihydroxyflavone (7,8-DHF, 10 mg/kg, i.p.), a selective TrkB receptor agonist, to activate the BDNF/TrkB signaling and examined its rapid-acting antidepressant-like effects; levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in BV2 microglial cells and synapse-related factors (BDNF, GluA1, Synapsin-1, and PSD95) in HT22 cells were examined by ELISA. Our behavioral results suggested that 7,8-DHF (10 mg/kg, i.p.) exerted rapid-acting antidepressant-like effects in Cort/LPS-treated mice; our immunofluorescence staining results suggested that Cort/LPS reduced the number of NeuN + HT22 cells and increased the number of Iba1 + BV2 microglial cells, which were completely reversed by 7,8-DHF pre-treatment. Our ELISA results suggested that 7,8-DHF significantly normalized the release of synapse-related factors (BDNF, GluA1, and PSD95) in HT22 cells and suppressed the production of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in BV2 microglial cells. Taken together, this study suggested that pharmacologically activating the BDNF/TrkB signaling pathway exerted rapid-acting antidepressant-like effects through improving synaptic plasticity and inhibiting neuroinflammation, which provided new insights for developing next-generation rapid-acting antidepressants.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"158"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium butyrate alleviates spinal cord injury via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis.","authors":"Yanru Cui, Qiuyu Cen, Jing Feng, Juanfang Wei, Linjie Wang, Cong Chang, Rizhao Pang, Junyu Wang, Anren Zhang","doi":"10.1007/s11011-025-01589-8","DOIUrl":"10.1007/s11011-025-01589-8","url":null,"abstract":"<p><p>NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific proteinase 1 (Caspase-1)/gasdermin D (GSDMD)-mediated pyroptosis is linked to spinal cord injury (SCI) pathogenesis. The levels of short-chain fatty acids (SCFAs), especially butyric acid, are significantly altered after SCI. Sodium butyrate (NaB) has anti-inflammatory effects on SCI; however, its effect on pyroptosis is unknown. The aim of this study was to determine the role of NaB in SCI functional recovery and its effect on NLRP3/Caspase-1/GSDMD-mediated pyroptosis. SCI model rats were established using aneurysm clips. After SCI, rats were administered NaB (300 mg/kg) via gavage. SCFAs in faeces were measured using gas chromatography-mass spectrometry. Motor function recovery was assessed using cylinder rearing and grooming tests. Histopathological analysis was performed using haematoxylin-eosin staining, transmission electron microscopy, and terminal deoxynucleotidyl transferase dUTP nick-end labelling. The expression of proteins associated with pyroptosis signalling pathways was analysed using enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. SCFAs levels, particularly butyric acid, significantly decreased after SCI. NaB treatment promoted forelimb motor function recovery and attenuated pathological SCI. NaB also decreased spinal pro-inflammatory factors (interleukin-18 and interleukin-1β) and downregulated pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein, Caspase-1, and GSDMD. NaB inhibits NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis and inflammation, exerting protective and therapeutic effects in SCI, suggesting NaB as an effective SCI treatment.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"157"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STC2 regulates the proliferation, migration and glycolysis of glioma cells through modulating ITGB2.","authors":"Zefeng Wei, Dengfeng Ge, Jie Bu, Xuenan Wang, Tao Zhong, Xiaoxiao Gongye, Bin Zhang, Feng Yan, Chunyan He, Runhan Guo, Jiayi Li, Zhenzhen Jin","doi":"10.1007/s11011-025-01571-4","DOIUrl":"https://doi.org/10.1007/s11011-025-01571-4","url":null,"abstract":"<p><p>Glioma is a common and aggressive primary malignant brain tumor. However, the progression mechanism of glioma has not been well revealed. In this study, we intend to detect the function and related mechanism of STC2 in glioma. Gene Expression Profiling Interactive Analysis database was used to detect STC2 and ITGB2 expression in glioma samples, as well as the relationship between STC2 and other genes. The relationship between STC2 and ITGB2 was confirmed by co-immunoprecipitation assay. The biology function of glioma cells was determined by cell counting kit-8, colony formation, transwell, ELISA and western blot assays. We discovered that STC2 was highly expressed in glioma samples and cell lines. Knocked down of STC2 inhibited cell proliferation, invasion, migration and glycolysis. Further analysis demonstrated the interaction between ITGB2 and STC2 as well as its involvement in STC2-regulated proliferation, invasion, migration and glycolysis. In summary, our data afforded novel insights into understanding the regulatory mechanism of STC2 and suggested that the STC2/ITGB2 axis might be a potential therapeutic target for glioma.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"156"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective mechanism of apigenin in proton pump inhibitor-associated progressive cognitive impairment in adult zebrafish via targeting GSK-3β pathway.","authors":"Anjalee Bhratee, Dhrita Chatterjee, Romanpreet Kaur, Shamsher Singh","doi":"10.1007/s11011-025-01579-w","DOIUrl":"https://doi.org/10.1007/s11011-025-01579-w","url":null,"abstract":"<p><p>Cognitive impairment is characterized by memory loss and difficulty in focusing, remembering, adhering to directions, and solving problems; commonly seen in an elderly population. Apigenin (APG) (4', 5, 7-trihydroxyflavone) is a flavonoid with several positive health benefits, including chemoprevention, antioxidant and can suppress inflammatory responses by inhibiting TNF-α and IL-1β levels. In this experimental study, we observed the possible neuroprotective effects of APG in the zebrafish model exposed to Lansoprazole (LPZ), a proton pump inhibitor known to induce cognitive impairment through hyperactivation of GSK-3β pathway. This experiment involves 12 adult zebrafish per group, where one group received LPZ (100 mg) as a toxin for 7 days and APG (25, 50, and 100 mg/kg) as treatment, while DPZ (5 mg/kg) served as a standard comparison over the same period. Neurobehavioral tests such as T-Maze, Novel Tank Test (NTT), and Novel Object Recognition (NOR) were performed. Several biochemical assessments were also performed to evaluate the level of lipid peroxidation (LPO), glutathione (GSH), nitrite (NO), acetylcholinesterase activity (AChEs), catalase activity, neurotransmitters (GABA and glutamate), neuroinflammatory markers (IL-1β, TNF-α, and IL-10), and histopathological analysis. The results showed that apigenin enhanced memory function, improved neurotransmitter balance, decreased oxidative stress markers, regulated the production of proinflammatory cytokines, and inhibited GSK-3β activity. Additionally, the co-administration of a GSK-3β inhibitor further promoted neuroprotection and cognitive enhancement facilitated by apigenin, highlighting the importance of the GSK-3β signaling pathway. These findings highlight the potential of apigenin as a natural compound for mitigating cognitive dysfunction. However, this study should also include long-term toxicity assessments and deeper molecular analysis to elucidate Apigenin's mechanism of action fully. Future research should address these gaps to validate its therapeutic potential.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"155"},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of Indole 3-carbinol against Scopolamine-Induced cognitive and memory impairment in rats: modulation of oxidative stress, inflammatory and cholinergic pathways.","authors":"Laksmi Anusha Vinjavarapu, Srikanth Yadava, Harikrishna Reddy Dontiboina, Guntupalli Chakravarthi, Ramakrishna Kakarla","doi":"10.1007/s11011-025-01577-y","DOIUrl":"https://doi.org/10.1007/s11011-025-01577-y","url":null,"abstract":"<p><p>Indole 3-carbinol (I3C), a natural compound found in cruciferous vegetables, has demonstrated neuroprotective effects by modulating oxidative stress, inflammation, and cholinergic pathways. This study aimed to evaluate the efficacy of I3C in preventing cognitive impairment induced by scopolamine in rats. Male Wistar rats were assigned to six groups: Control, Scopolamine (1 mg/kg), I3C (25 mg/kg), I3C (50 mg/kg), I3C (100 mg/kg), and Donepezil (5 mg/kg). Memory function was evaluated through behavioral assessments using the Y-maze and Novel Object Recognition (NOR) tests. Biochemical analyses were conducted to assess acetylcholinesterase (AChE) activity and oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). ELISA were utilized to quantify oxidative stress regulators (NRF2 and HO-1), inflammatory cytokines (NF-kB, TNF-α, IL-6, and IL-10), and apoptosis-related markers (Cytochrome C, caspase 9, and caspase 3). Additionally, H&E and Nissl staining were performed to evaluate histopathological abnormalities. The findings revealed that I3C administration markedly enhanced cognitive performance in the Y-maze and NOR tests, which were attributed to decreased AChE activity and increased acetylcholine (ACh) levels. Furthermore, I3C significantly alleviated oxidative stress by upregulating antioxidant enzymes, including NRF2 and HO-1. Moreover, I3C mitigated inflammatory responses, as evidenced by elevated levels of IL-10 and reduced levels of NF-kB, TNF-α, and IL-6. These findings indicate that I3C exhibits neuroprotective effects by reducing oxidative stress, suppressing inflammation, and addressing abnormalities in the cholinergic pathway, highlighting its potential as a therapeutic approach for alleviating cognitive deficits.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"154"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of omega-3 against procarbazine-induced brain damage in the cerebellum and CA1 Hippocampus of male rats: a focus on oxidative stress mechanisms.","authors":"Maryam Abolghasemi, Ali Shamsara, Masoumeh Nozari, Rana Eftekhar-Vaghefi, Masoumeh Baghalishahi, Ali Sarhadi Roodbari, Mohammad Reza Afarinesh","doi":"10.1007/s11011-025-01575-0","DOIUrl":"10.1007/s11011-025-01575-0","url":null,"abstract":"<p><p>The study examined the combined effects of procarbazine (PCZ) and omega-3 on cognitive functions, motor skills, and brain histology in male rats over ten days. While PCZ has antitumor properties, omega-3 is a dietary supplement with potential health benefits. Here, forty-eight adult male Wistar rats, averaging 230 to 250 g, were used in this study. Novel Object Recognition (NOR), Open Field Tests (OFT), and rotarod assessments were employed to evaluate cognitive and motor functions. Also, cell degeneration in pyramidal cells of the CA1 region and Purkinje cells in the cerebellum, along with measuring serum oxidant and antioxidant levels to gauge treatment impact on brain functions. Results showed significant weight loss in PCZ-treated rats, alongside fewer rearing instances and reduced distance traveled in OFT compared to the sham group (P < 0.05). However, cognitive performance in the NOR test remained unchanged. The PCZ group demonstrated lower rotarod performance than the sham group (P < 0.05), but the PCZ + omega-3 group showed improved balance. Antioxidant enzyme levels decreased in the PCZ group relative to the sham group (P < 0.05), with no significant change in malondialdehyde levels; omega-3 did not influence these levels in PCZ-treated rats. PCZ caused damage to pyramidal cells in the hippocampus and cerebellum, but omega-3 mitigated some of the cerebellar damage, suggesting it may partially reduce PCZ-induced toxicity. These findings suggest omega-3 could alleviate some negative effects of PCZ on brain functions, especially in the cerebellum.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 3","pages":"153"},"PeriodicalIF":3.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic pathways and genes involved in treatable and non-treatable metabolic epilepsies. A comprehensive review and metabolic pathway analysis.","authors":"Athanasia Sesse, Paris Ladias, Charilaos Kostoulas, Dimitrios Chatzistefanidis, Ioannis Georgiou, Sofia Markoula","doi":"10.1007/s11011-025-01562-5","DOIUrl":"10.1007/s11011-025-01562-5","url":null,"abstract":"<p><p>More than 600 different metabolic disorders can lead to a clinical picture, where seizures are a main neurological manifestation, either as the primary clinical finding or as a part of a more complex phenotype. For these metabolic disorders, the term \"metabolic epilepsy\" is commonly used. About one in six metabolic epilepsies is treatable, constituting a well-defined subset of metabolic disorders, which is amenable to treatment targeting the primary cause of the seizures and reducing or preventing associated complications. However, the majority of metabolic disorders currently lack effective treatment, making them a major challenge both in clinical practice and in research. Herein, we provide an overview of both treatable and non-treatable metabolic epilepsies and discuss our current understanding of these disorders. We also perform pathway analysis in order to compare the pathways in which the genes associated with treatable and non-treatable metabolic epilepsies take part. This approach may orientate the research to particular pathways and explore novel treatment algorithms.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 3","pages":"152"},"PeriodicalIF":3.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a mitochondrial calcium uniporter and P-selectin inhibitors on neural injury induced by global cerebral ischemia-reperfusion in male rats.","authors":"Setareh Javanmardi, Farshad Moradpour, Mojgan Veisi, Neda Omidian, Rasoul Kavyannejad","doi":"10.1007/s11011-025-01570-5","DOIUrl":"10.1007/s11011-025-01570-5","url":null,"abstract":"<p><p>Neural injury following ischemia-reperfusion (I/R) is induced by multiple pathophysiological pathways. This study aimed to use mitochondrial calcium channel and p-selectin inhibitors to weaken these pathways. One hundred and two rats were randomly divided into six groups. In the sham group, cerebral I/R induction and drug intervention were not performed. In the I/R group, cerebral I/R induction was induced. In the RR + FCN group, animals received only ruthenium red (RR) and fucoidan (FCN) intraperitoneally without I/R induction. In the I/R + RR group, animals received RR during the cerebral I/R period. In the I/R + FCN group, FCN was administered along with cerebral I/R. In the I/R +(RR + FCN) group, animals exposed to cerebral I/R received a combination of RR and FCN simultaneously. The shuttle box and new object tests were used to assess learning and memory. The superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels in the hippocampus were measured. Neuronal death in the hippocampal CA1 area was assessed via hematoxylin-eosin staining. FCN and RR significantly decreased the tissue MDA, IL-1β, TNF-α levels while increased the SOD level. These inhibitors significantly reduced learning disorders and cerebral edema following I/R. The rate of neuronal death was significantly lower in each of the receiving RR and FCN groups. This study revealed that the use of FCN and RR significantly attenuated the pathways associated with oxidative stress and inflammation as well as neuronal death following cerebral I/R, thereby reducing learning and memory impairments. The effects of neuroprotection were further determined when two inhibitors were used simultaneously. HIGHLIGHTS: Cerebral ischemia-reperfusion is associated with many neurological, sensory and motor defects. Multiple pathways of neural pathophysiology are activated during cerebral ischemia-reperfusion. The Administration of ruthenium and fucoidan weakens inflammatory pathways, oxidative stress, and learning dysfunctions caused by cerebral ischemia and reperfusion. Stronger Neuroprotective effects were observed during the simultaneous administration of ruthenium and fucoidan.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 3","pages":"150"},"PeriodicalIF":3.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of quercetin and derivatives on NAMPT/Sirtuin-1 metabolic pathway in neuronal cells: an approach to mitigate chemotherapy-induced cognitive impairment.","authors":"Jeena John, Subham Das, Anu Kunnath, Jayesh Mudgal, Krishnadas Nandakumar","doi":"10.1007/s11011-025-01567-0","DOIUrl":"10.1007/s11011-025-01567-0","url":null,"abstract":"<p><strong>Background: </strong> The cognitive alterations observed in individuals undergoing cancer treatments have garnered more attention recently. Chemotherapy can reduce nicotinamide adenine dinucleotide (NAD+) levels by inhibiting nicotinamide phosphoribosyl transferase (NAMPT). This reduction can make cancer cells more susceptible to oxidative damage and death and may also affect non-cancerous cells, particularly the brain cells. During chemotherapy-induced suppression, the downregulation of the NAMPT-mediated NAD+/Sirtuin 1 (SIRT1) pathway may cause dyscognition. Objective: This study aimed to assess the role of quercetin and analogues in chemobrain and the associated mechanisms. Methods: The potential of quercetin and its derivatives interaction with NAMPT and SIRT1 proteins was performed using computational studies followed by their in vitro evaluation in SH-SY5Y cells. Molecular docking and simulation studies of human SIRT1 and NAMPT proteins with quercetin and its derivatives were performed. Differentiated SH-SY5Y cell lines were treated with quercetin and selected derivatives against Methotrexate and 5-Fluorouracil (MF) toxicity, by subjecting to cytotoxicity assay, flow cytometry, and RT-PCR analysis. Results: Quercetin, Rutin, and Isoquercetin showed interactions necessary in the activation process of both proteins. Cytotoxicity and flow cytometric studies demonstrated that the phytochemicals shield the differentiated SH-SY5Y cells from MF toxicity. As determined by RT-PCR investigations, NAMPT and SIRT1 gene mRNA expression was higher in test drug-treated cells at quercetin (0.12, 0.6 µM), rutin, and isoquercetin (16, 80 µM) and lower in MF-treated cells. Conclusion: The treatment of phytochemicals alleviated CICI by targeting NAMPT and SIRT1 proteins, which could lead to the identification of effective treatment strategies for the chemobrain.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 3","pages":"151"},"PeriodicalIF":3.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin inhibited chronic unpredictable mild stress-induced mouse depressive behaviors through attenuating lateral Habenula neuronal activities.","authors":"Yu-Ting Cai, Dong-Ni Chen, Ke-Xin Li, Jia-Jia Dong, Chong Li, Ying-Kui Liu, Yong Liu","doi":"10.1007/s11011-025-01569-y","DOIUrl":"10.1007/s11011-025-01569-y","url":null,"abstract":"<p><p>As a flavonoid, quercetin has shown anti-tumor, anti-inflammation, and anti-depressant effects. However, the exact anti-depressant mechanism of quercetin remains unclear. In this study, a combination of behavioral tests and neuropharmacological methods were used to investigate whether the endocannabinoid (eCB) system in the lateral habenula (LHb) mediated the anti-depressant pathogenesis of quercetin. Depressive model was prepared by chronic unpredictable mild stress (CUMS) in C57 mice. The CUMS exposure led to depressive-like behaviors and an increase of the miniature excitatory postsynaptic current (mEPSC) frequency in the LHb neurons, which were blocked by quercetin intragastrically administered for 14 days. As quercetin has been shown to upregulate the mRNA expression of cannabinoid receptor 1 (CB1) in cultured tumor cells, and the inhibitory effect of eCB system activation is related to glutamatergic neurons, depolarization-induced suppression of excitation (sDSE) was detected. The results showed that presynaptic inhibitory effect of eCB system was significantly down-regulated in the LHb of CUMS model, and the down-regulation was abolished by quercetin. Blocking eCB system in the LHb with CB1 antagonist AM251 rescued the neuroprotective effects of quercetin in CUMS mice. Taken together, the results suggested that eCB system in the LHb was involved in the anti-depressant effects of quercetin.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 3","pages":"149"},"PeriodicalIF":3.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}