{"title":"The effect of 3-di-o-tolylguanidine on the level of neurotransmitters in the cerebellum and related disorders of social behavior.","authors":"Agnieszka Piechal, Kamilla Blecharz-Klin, Alicja Jakimiuk, Justyna Pyrzanowska, Ilona Joniec-Maciejak, Dagmara Mirowska-Guzel, Ewa Widy-Tyszkiewicz","doi":"10.1016/j.neuroscience.2024.12.017","DOIUrl":"10.1016/j.neuroscience.2024.12.017","url":null,"abstract":"<p><p>It is common knowledge that the cerebellum is a structure of the central nervous system that influences the processes of balance and motor coordination. Recently its influence on social interactions has also been emphasized. The sigma receptor agonist: 3-di-o-tolylguanidine (DTG) is characterized by high affinity for sigma 1 and sigma 2 receptors, widely distributed in the cerebellum. In the experiment we assessed the effect of long term administration of DTG to adult male Sprague Dawley rats on social behavior and the concentration of neurotransmitters in the cerebellum. DTG was administered orally at a dose of 3 mg/kg body weight (bw) (DTG3), 10 mg/kg bw (DTG10) and 30 mg/kg bw (DTG30) for 9 weeks before the behavioral test. After the experiment, the concentration of catecholamines and amino acids in the cerebellum was assessed using high performance liquid chromatography (HPLC). Treatment groups showed reductions in social interactions such as grooming, sniffing and total time spent interacting. At the same time, it was shown that in the group receiving the lowest dose of the drug, a decrease in the concentration of dopamine and serotonin in the cerebellum was observed. Furthermore, changes in the concentration of taurine, alanine, glutamic acid and gamma-aminobutyric acid were observed in the treated groups. We found that long term administration of DTG disturbs animals' social interactions and the concentration of neurotransmitters in the cerebellum.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"549-557"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854754","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":"Co-occurrence of Parkinson's disease and Retinitis Pigmentosa: A genetic and in silico analysis.","authors":"Archana Dwivedi, Anand Kumar, Mohammed Faruq, Varun Kumar Singh, Nidhi Dwivedi, Kamaljeet Singh, Ibrahim Hussain, Swati Parida, Gaurab Kumar Jha, Niraj Kumar, Deepika Joshi","doi":"10.1016/j.neuroscience.2024.12.019","DOIUrl":"10.1016/j.neuroscience.2024.12.019","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) is primarily driven by the protein Alpha Synuclein (A-Syn) accumulation. Synphilin-1 protein, encoded by the SNCAIP gene, which co-localizes with A-Syn is a known risk factor for PD. Retinitis pigmentosa (RP), is a cluster of retinal degenerative disorders, and Cyclic Nucleotide Gated channel subunit Alpha 1 (CNGA1) is one of the initial genes associated with RP. Patients with PD can have various kinds of visual dysfunction as a non-motor manifestation, but to date, CNGA1 mutation and RP as a PD associated visual symptom has not been reported. We report a mutation in the SNCAIP gene in a PD patient, not reported earlier, and its co-occurrence with RP-associated CNGA1 gene mutation.</p><p><strong>Method: </strong>Whole exome sequencing (WES) of the patient DNA sample and in-silico protein-protein interaction (PPI) analysis performed to find out proteins interacting with SNCAIP relevant concerning reported mutation of SNCAIP and further, CNGA1 interaction with SNCAIP.</p><p><strong>Result: </strong>We are reporting, a missense mutation (p.Thr64Ser) at the SNCAIP gene, co-occurring with a missense variation (p.Gly509Arg) in the CNGA1 gene. In silico PPI analysis suggests SIAH1 as an important protein affected by SNCAIP mutation. LGALS4 and SNCA (gene encoding A-Syn) are common interactors between SNCAIP and CNGA1.</p><p><strong>Conclusion: </strong>The current study has determined the co-occurrence of RP and PD, whole exome sequencing ascertains the mutations in SNCAIP and CNGA1 genes, which could be the cause of PD and RP co-occurrence.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"519-526"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824384","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}
NeurosciencePub Date : 2025-01-26Epub Date: 2024-12-02DOI: 10.1016/j.neuroscience.2024.11.076
Duan Li, Anthony G Hudetz
{"title":"Anesthesia alters complexity of spontaneous and stimulus-related neuronal firing patterns in rat visual cortex.","authors":"Duan Li, Anthony G Hudetz","doi":"10.1016/j.neuroscience.2024.11.076","DOIUrl":"10.1016/j.neuroscience.2024.11.076","url":null,"abstract":"<p><p>Complexity of neuronal firing patterns may serve as an indicator of sensory information processing across different states of consciousness. Recent studies have shown that spontaneous changes in brain states can occur during general anesthesia, which may influence neuronal complexity and the state of consciousness. In this study, we investigated how the firing patterns of cortical neurons, both at rest and during visual stimulation, are affected by spontaneously changing brain states under varying levels of anesthesia. Extracellular unit activity was measured in the primary visual cortex of unrestrained rats as the inhaled concentration of desflurane was incrementally reduced to 6%, 4%, 2%, and 0%. Using dimensionality reduction and density-based clustering on individual unit activities, we identified five distinct population states, which underwent dynamic transitions independent of the anesthetic level during both resting and stimulus conditions. One population state that occurred mainly in deep anesthesia exhibited a paradoxically increased number of active neurons and asynchronous spiking, suggesting a spontaneous reversal towards an awake-like condition. However, this was contradicted by the observation of low neuronal complexity in both spontaneous and stimulus-related spike activity, which more closely aligns with unconsciousness. Our findings reveal that transient neuronal states with distinct spiking patterns can emerge in visual cortex at constant anesthetic concentrations. The reduced complexity in states associated with deep anesthesia likely indicates a disruption of conscious sensory information processing.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"440-456"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780519","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}
NeurosciencePub Date : 2025-01-26Epub Date: 2024-12-14DOI: 10.1016/j.neuroscience.2024.12.023
Narjes Baazaoui, Mohammad Y Alfaifi, Rania Ben Saad, Stefania Garzoli
{"title":"Potential role of long noncoding RNA maternally expressed gene 3 (MEG3) in the process of neurodegeneration.","authors":"Narjes Baazaoui, Mohammad Y Alfaifi, Rania Ben Saad, Stefania Garzoli","doi":"10.1016/j.neuroscience.2024.12.023","DOIUrl":"10.1016/j.neuroscience.2024.12.023","url":null,"abstract":"<p><p>Neurodegenerative diseases (ND) are complex diseases of still unknown etiology. Lately, long non-coding RNAs (lncRNAs) have become increasingly popular and implicated in several pathologies as they have several roles and appear to be involved in all biological processes such as cell signaling and cycle control as well as translation and transcription. MEG3 is one of these and acts by binding proteins or directly or competitively binding miRNAs. It has a crucial role in controlling cell death, inflammatory process, oxidative stress, endoplasmic reticulum stress, epithelial-mesenchymal transition and other processes. Recent reports showed that MEG3 is a major driving force of the necrosis phenomena in AD, causing the death of neurons, and its upregulation in cancer patients was linked to tumor suppression. Dysregulation of MEG3 affects neuronal cell death, inflammatory process, smooth muscle cell proliferation and consequently leads to the initiation or the acceleration of the disease. This review examines the current state of knowledge concerning the level of expression and the regulatory function of MEG3 in relation to several NDs. In addition, we examined the relation of MEG3 with neurotrophic factors such as Tumor growth factor β (TGFβ) and its possible mechanism of action. A comprehensive and in-depth analysis of the role of MEG3 in ND could give a clearer picture about the initiation of the process of neuronal death and help develop an alternative therapy that targets MEG3.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"487-498"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829532","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}
NeurosciencePub Date : 2025-01-26Epub Date: 2024-11-26DOI: 10.1016/j.neuroscience.2024.11.060
Yu Ting Liu, Yu Ting Yang, Chun Xiang Tang, Jun Qing Ma, Xiang Kong, Jian Hua Li, Yan Ming Li, Shu Yu Liu, Chang Sheng Zhou, Long Jiang Zhang
{"title":"Brain structural and functional changes in patients with chronic heart failure.","authors":"Yu Ting Liu, Yu Ting Yang, Chun Xiang Tang, Jun Qing Ma, Xiang Kong, Jian Hua Li, Yan Ming Li, Shu Yu Liu, Chang Sheng Zhou, Long Jiang Zhang","doi":"10.1016/j.neuroscience.2024.11.060","DOIUrl":"10.1016/j.neuroscience.2024.11.060","url":null,"abstract":"<p><p>Heart failure (HF) frequently suffers from brain abnormalities and cognitive impairments. This study aims to investigate brain structure and function alteration in patients with chronic HF. This retrospective study included 49 chronic HF and 49 health controls (HCs). Voxel-based morphometry was conducted on structural MRI to quantify gray matter volume (GMV), and functional connectivity (FC) was assessed with seed-based analysis using resting-state fMRI. White matter microstructure integrity was also evaluated through tract-based spatial statistics employing DTI. Correlations between multimodal MRI features and cognitive performance were further investigated in patients with chronic HF. Patients with chronic HF exhibited significantly reduced regional GMV, white matter microstructure injury (Family wise error correction, p<0.05), and decreased FC in multiple brain regions involved in cognition, sensorimotor, visual function (Gaussian random field correction, voxel level p<0.0001 and cluster-level p<0.01). There was no observed increases in GMV or FC compared with HCs. Decreased GMV showed positive correlations with cognitive performance (r = 0.025-0.577, p = 0.025-0.001), while decreased fractional anisotropy was negatively correlated with anxiety scores (r = -0.339, p = 0.040) in patients with chronic HF. This study revealed that patients with chronic HF exhibited brain structure injury affecting gray matter and white matter, as well as FC abnormalities of brain regions responsible for cognition, sensorimotor and visual function. These findings suggest GMV could serve as a neuroimaging biomarker for cognitive impairments and a potential target for neuroprotective therapies in patients with chronic HF.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"148-154"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739929","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":"Anxiety in aquatics: Leveraging machine learning models to predict adult zebrafish behavior.","authors":"Vartika Srivastava, Anagha Muralidharan, Amrutha Swaminathan, Alwin Poulose","doi":"10.1016/j.neuroscience.2024.12.013","DOIUrl":"10.1016/j.neuroscience.2024.12.013","url":null,"abstract":"<p><p>Accurate analysis of anxiety behaviors in animal models is pivotal for advancing neuroscience research and drug discovery. This study compares the potential of DeepLabCut, ZebraLab, and machine learning models to analyze anxiety-related behaviors in adult zebrafish. Using a dataset comprising video recordings of unstressed and pre-stressed zebrafish, we extracted features such as total inactivity duration/immobility, time spent at the bottom, time spent at the top and turn angles (large and small). We observed that the data obtained using DeepLabCut and ZebraLab were highly correlated. Using this data, we annotated behaviors as anxious and not anxious and trained several machine learning models, including Logistic Regression, Decision Tree, K-Nearest Neighbours (KNN), Random Forests, Naive Bayes Classifiers, and Support Vector Machines (SVMs). The effectiveness of these machine learning models was validated and tested on independent datasets. We found that some machine learning models, such as Decision Tree and Random Forests, performed excellently to differentiate between anxious and non-anxious behavior, even in the control group, where the differences between subjects were more subtle. Our findings show that upcoming technologies, such as machine learning models, are able to effectively and accurately analyze anxiety behaviors in zebrafish and provide a cost-effective method to analyze animal behavior.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"577-587"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829531","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}
NeurosciencePub Date : 2025-01-26Epub Date: 2024-12-07DOI: 10.1016/j.neuroscience.2024.12.011
Houying Fang, Hao Tian, Jianlin Liu, Tao Peng, Dan Wang
{"title":"Ginsenoside Rg1 attenuates Aβ<sub>1-42</sub>-induced microglial cell apoptosis and inflammation in Alzheimer's disease via the GATA4/PDE4A/PI3K/AKT axis.","authors":"Houying Fang, Hao Tian, Jianlin Liu, Tao Peng, Dan Wang","doi":"10.1016/j.neuroscience.2024.12.011","DOIUrl":"10.1016/j.neuroscience.2024.12.011","url":null,"abstract":"<p><p>Ginsenoside Rg1 (Rg1) has been shown to treat a variety of human diseases, including Alzheimer's disease (AD). However, its mechanism in AD needs further investigation. Microglial cells (BV2) were treated with Aβ<sub>1-42</sub> to induce AD cell models. Cell viability and apoptosis were tested by cell counting kit 8 assay and flow cytometry. The protein levels of GATA-binding protein 4 (GATA4), phosphodiesterase 4A (PDE4A), autophagy-related markers, M1/M2 polarization-related markers and PI3K/AKT-related markers were detected by western blot. Inflammation factors were detected by ELISA. Jaspar and dual-luciferase reporter assay were used to evaluate the interaction between GATA4 and PDE4A. Our results showed that Rg1 promoted viability and autophagy, while suppressed apoptosis and inflammation in Aβ<sub>1-42</sub>-induced BV2 cells. Rg1 reduced GATA4 protein expression, and GATA4 upregulation reversed the regulation of Rg1 on Aβ<sub>1-42</sub>-induced BV2 cell injury. GATA4 interacted with PDE4A, and GATA4 facilitated Aβ<sub>1-42</sub>-induced BV2 cell injury by increasing PDE4A expression. Besides, GATA4 knockdown reduced PDE4A protein expression and inactivated PI3K/AKT axis, while these effects were abolished by PDE4A overexpression. In conclusion, our data suggested that Ginsenoside Rg1 inhibited microglial cell apoptosis and inflammation to attenuate AD progression by regulating the GATA4/PDE4A/PI3K/AKT axis.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"377-385"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801764","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":"Whole-brain functional connectivity and structural network properties in stroke patients with hemiplegia.","authors":"Xuejin Cao, Zan Wang, Hongxing Wang, Hengrui Zhou, Jia Quan, Xiaohui Chen, Xi Yang, Shenghong Ju, Yuancheng Wang, Yijing Guo","doi":"10.1016/j.neuroscience.2024.12.016","DOIUrl":"10.1016/j.neuroscience.2024.12.016","url":null,"abstract":"<p><strong>Objective: </strong>This study explored structural and functional alterations in the whole brain of stroke patients with hemiplegia.</p><p><strong>Methods: </strong>We collected multimodal magnetic resonance images of 24 patients with ischaemic stroke and 16 age-matched controls. Resting-state functional connectivity (FC) for all brain regions was evaluated. Diffusion tensor imaging was used to construct white matter structural networks, and the graph properties of the structural network were analysed using graph theory to determine group differences.</p><p><strong>Results: </strong>The ipsilesional posterior parietal cortex (PPC) in the frontoparietal network accounts for more than half of the 25 brain regions with altered FC in stroke patients. The nodal efficiency of multiple ipsilesional frontal lobes and cerebellar regions, such as the ipsilateral cerebellum 8, was reduced. The contralesional cerebellum 8 showed elevated FC with the lingual gyrus and the visual network.</p><p><strong>Conclusions: </strong>Our results suggest that the PPC and cerebellum 8 are regions worthy of in-depth study. The cerebellum 8 may supplement deficits in motor balance function by enhancing functional congruence with the visual area.</p><p><strong>Significance: </strong>This study identified key brain regions and characteristics that exhibit structural and functional changes following stroke injury.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"420-430"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813703","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}
NeurosciencePub Date : 2025-01-26Epub Date: 2024-12-04DOI: 10.1016/j.neuroscience.2024.12.005
Su Yu, Xinyan Zhang, Yan-Gang Sun
{"title":"Peripheral and central innervation pattern of mechanosensory neurons in the trigeminal ganglion.","authors":"Su Yu, Xinyan Zhang, Yan-Gang Sun","doi":"10.1016/j.neuroscience.2024.12.005","DOIUrl":"10.1016/j.neuroscience.2024.12.005","url":null,"abstract":"<p><p>The trigeminal ganglion (TG) comprises primary sensory neurons responsible for orofacial sensations, subsequently projecting to the trigeminal nuclei in the brainstem. However, the circuit basis of nasal mechanosensation is not well characterized. Here we elucidate the anatomical organization of both peripheral and central projections of the TG. We found that the non-peptidergic nociceptor, MAS-related G protein-coupled receptor member D positive (MrgprD<sup>+</sup>) neurons in the TG densely innervate the nasal mucosa, whereas the low-threshold mechanoreceptors subtypes rarely innervate the nasal mucosa. We also identified the central projection pattern of the mechanosensory neurons in TG. The tyrosine kinase receptor C positive (TrkC<sup>+</sup>) neurons, tyrosine kinase receptor B positive (TrkB<sup>+</sup>) and tyrosine hydroxylase positive (TH<sup>+</sup>) neurons project to multiple subregions of brainstem trigeminal complex and solitary nucleus. In contrast, the MrgprD<sup>+</sup> neurons only densely project to outer edge of Sp5C. In addition, we further determined the ascending pathway of the TG neurons. Taken together, our study demonstrates the peripheral and central projection pattern of mechanosensory neurons in the TG, which provides a basis for the future functional studies.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"558-566"},"PeriodicalIF":2.9,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792024","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":"Metformin attenuated depressive-like behaviors by suppressing TRPV1/NLRP3 mediated neuroinflammation in the hypothalamus of allergic rhinitis mice.","authors":"Yunfei Wang, Yulie Xie, Peiqiang Liu, Hao Lv, Mengting Guan, Jianchao Cong, Yan Wang, Yu Xu","doi":"10.1016/j.neuroscience.2025.01.043","DOIUrl":"https://doi.org/10.1016/j.neuroscience.2025.01.043","url":null,"abstract":"<p><strong>Background: </strong>In addition to nasal symptoms, allergic rhinitis (AR) has increasingly been reported to be associated with depression-like behaviors. Recent evidence suggests that neuroinflammation in the hypothalamus may cause these depressive symptoms in AR. However, the precise mechanisms and effective treatments remain to be elucidated.</p><p><strong>Objective: </strong>This study investigated the ameliorative effects of metformin on neuroinflammation in the hypothalamus, depressive-like behavior and the underlying molecular mechanisms of AR mice.</p><p><strong>Methods: </strong>Mice were administered ovalbumin (OVA) intranasally to induce allergic rhinitis and subsequently subjected to behavioral experiments to detect depressive-like behavior. The roles of the TRPV1/NLRP3 pathway in depression-like behaviors in AR were examined in vivo. Additionally, the mechanism of TRPV1/NLRP3-mediated neuroinflammation was investigated in vitro. Finally, metformin was utilized to explore its possible mechanisms and efficacy in treating depressive-like behavior in AR.</p><p><strong>Results: </strong>AR mice exhibited significant depressive-like behavior, which was attenuated by metformin. The number of Iba-1<sup>+</sup> microglia significantly increased in the hypothalamus of AR mice. The expression of NLRP3 was significantly upregulated in the hypothalamus, activating microglia. Metformin ameliorated the neuropsychiatric symptoms by reducing NLRP3 expression in the hypothalamus. Moreover, metformin inhibited LPS-induced upregulation of the TRPV1/NLRP3 signaling pathway in microglial cell line, an effect that can be reversed by the TRPV1-specific agonist capsaicin.</p><p><strong>Conclusion: </strong>Increased TRPV1 expression activates the NLRP3 inflammasome in hypothalamic microglia, promoting the pathological process of depressive-like behavior in AR mice. Metformin could effectively treat neuroinflammation by regulating microglia via TRPV1 downregulation, indicating its potential as a treatment for depressive-like behaviors in AR.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029170","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}