{"title":"Microtubules, Membranes, and Movement: New Roles for Stathmin-2 in Axon Integrity","authors":"Emma J. C. Thornburg-Suresh, Daniel W. Summers","doi":"10.1002/jnr.25382","DOIUrl":"https://doi.org/10.1002/jnr.25382","url":null,"abstract":"<p>Neurons establish functional connections responsible for how we perceive and react to the world around us. Communication from a neuron to its target cell occurs through a long projection called an axon. Axon distances can exceed 1 m in length in humans and require a dynamic microtubule cytoskeleton for growth during development and maintenance in adulthood. Stathmins are microtubule-associated proteins that function as relays between kinase signaling and microtubule polymerization. In this review, we describe the prolific role of Stathmins in microtubule homeostasis with an emphasis on emerging roles for Stathmin-2 (Stmn2) in axon integrity and neurodegeneration. Stmn2 levels are altered in Amyotrophic Lateral Sclerosis and loss of Stmn2 provokes motor and sensory neuropathies. There is growing potential for employing Stmn2 as a disease biomarker or even a therapeutic target. Meeting this potential requires a mechanistic understanding of emerging complexity in Stmn2 function. In particular, Stmn2 palmitoylation has a surprising contribution to axon maintenance through undefined mechanisms linking membrane association, tubulin interaction, and axon transport. Exploring these connections will reveal new insight on neuronal cell biology and novel opportunities for disease intervention.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165695","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":"The Endocannabinoid System in Alzheimer's Disease: A Network Meta-Analysis","authors":"Yu Liu, Hang Xing, Yan Zhang, Yi Song","doi":"10.1002/jnr.25380","DOIUrl":"10.1002/jnr.25380","url":null,"abstract":"<div>\u0000 \u0000 <p>The findings concerning the association between endocannabinoid system (ECS) and Alzheimer's disease (AD) exhibited inconsistencies when examining the expression levels of endocannabinoids. This study aimed to provide a comprehensive summary of the studies regarding alterations of the ECS in AD. Six databases were thoroughly searched for literature to select relevant studies investigating the ECS in AD, including changes in cannabinoid receptors (CB1R and CB2R), endocannabinoids (2-AG and AEA), and their associated enzymes (FAAH and MAGL). Traditional meta-analysis evaluated the expression levels of the ECS in AD, and the results showed no significant differences in ECS components between healthy controls and AD patients. However, subgroup analysis revealed significantly lower expression levels of CB1R in AD than in controls, particularly in studies using western blot (SMD = −0.88, <i>p</i> < 0.01) and in studies testing CB1R of frontal cortex (SMD = −1.09, <i>p</i> < 0.01). For studies using HPLC, the subgroup analysis indicated significantly higher 2-AG levels in AD than in controls (SMD = 0.46, <i>p</i> = 0.02). Network meta-analysis examined the rank of ECS alterations in AD compared to controls, and the findings revealed that 2-AG and MAGL exhibited the largest increase and CB1R showed the largest decrease relative to the control group. Based on the findings of traditional meta-analysis and network meta-analysis, we proposed that AD patients may present decreased expression levels of CB1R and increased expression levels of 2-AG and its degrading enzyme MAGL. Our results may contribute to the growing body of research supporting the therapeutic potential of ECS modulation in the management of AD.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154398","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":"Immune Cells Promote BDNF Expression by Infiltrated Macrophages via Interleukin 4 in the Cerebral Ischemia of Male Rats","authors":"Xiaobo Li, Yunqian Guan, Danni Chen, Jiyu Li, Wenxiu Yu, Haiqiang Zou, Bochao Liu, Ling Chen, Zhiguo Chen","doi":"10.1002/jnr.25379","DOIUrl":"10.1002/jnr.25379","url":null,"abstract":"<div>\u0000 \u0000 <p>We reported that infiltrated Ly6C<sup>+</sup> macrophages express brain-derived neurotrophic factor (BDNF) only at the cerebral cortex infarct in a rat dMCAO model. However, the changein neuron-expressed BDNF, the niche components that induce the Ly6C<sup>+</sup> cells to express BDNF, and the cellular sources of these components, remain unclear. In this study, immunofluorescence double staining was performed to label BDNF and Ly6C on brain sections at 3, 24, and 48 h following distal middle cerebral artery occlusion (dMCAO) of male rats, and to stain BDNF with Ly6C, IL-4R, and IL-10R. A neutralizing anti-IL-4 antibody was injected into the infarct, and the IL-4 and BDNF concentrations in the subareas of the infarct were determined using enzyme-linked immunosorbent assay. To find out the cellular sources of IL-4, the markers for microglia, T cells, and neurons were co-stained with IL-4 separately. In certain infarct subareas, the main BDNF-expressing cells shifted quickly from NeuN<sup>+</sup> neurons to Ly6C<sup>+</sup> cells during 24–48 h post-stroke, and the Ly6C<sup>+</sup>/BDNF<sup>+</sup> cells mostly expressed IL-4 receptor. Following IL-4 neutralizing antibody injection, the BDNF, IL-4 protein levels, and BDNF<sup>+</sup>/Ly6C<sup>+</sup> cells decreased significantly. The main IL-4-expressing cell type in this infarct subarea is not neuron either, but immune cells, including microglia, monocyte, macrophages, and T cells. The neurons, maintained BDNF and IL-4 expression in the peri-infarct area. In conclusion, in a specific cerebral subarea of the rat dMCAO model, IL-4 secreted by immune cells is one of the main inducers for Ly6C<sup>+</sup> cells to express BDNF.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132978","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}
Eunkyung Kim, Seo Jung Yun, Byung-Mo Oh, Han Gil Seo
{"title":"Impact of Electric Field Magnitude in the Left Dorsolateral Prefrontal Cortex on Changes in Intrinsic Functional Connectivity Using Transcranial Direct Current Stimulation: A Randomized Crossover Study","authors":"Eunkyung Kim, Seo Jung Yun, Byung-Mo Oh, Han Gil Seo","doi":"10.1002/jnr.25378","DOIUrl":"10.1002/jnr.25378","url":null,"abstract":"<p>This study investigated whether the electric field magnitude (E-field) delivered to the left dorsolateral prefrontal cortex (L-DLPFC) changes resting-state brain activity and the L-DLPFC resting-state functional connectivity (rsFC), given the variability in tDCS response and lack of understanding of how rsFC changes. Twenty-one healthy participants received either 2 mA anodal or sham tDCS targeting the L-DLPFC for 10 min. Brain imaging was conducted before and after stimulation. The fractional amplitude of low-frequency fluctuation (fALFF), reflecting resting brain activity, and the L-DLPFC rsFC were analyzed to investigate the main effect of tDCS, main effect of time, and interaction effects. The E-field was estimated by modeling tDCS-induced individual electric fields and correlated with fALFF and L-DLPFC rsFC. Anodal tDCS increased fALFF in the left rostral middle frontal area and decreased fALFF in the midline frontal area (FWE <i>p</i> < 0.050), whereas sham induced no changes. Overall rsFC decreased after sham (positive and negative connectivity, <i>p</i> = 0.001 and 0.020, respectively), with modest and nonsignificant changes after anodal tDCS (<i>p</i> = 0.063 and 0.069, respectively). No significant differences in local rsFC were observed among the conditions. Correlations were observed between the E-field and rsFC changes in the L-DLPFC (<i>r</i> = 0.385, <i>p</i> = 0.115), left inferior parietal area (<i>r</i> = 0.495, <i>p</i> = 0.037), and right lateral visual area (<i>r</i> = 0.683, <i>p</i> = 0.002). Single-session tDCS induced resting brain activity changes and may help maintain overall rsFC. The E-field in the L-DLPFC is associated with rsFC changes in both proximal and distally connected brain regions to the L-DLPFC.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120068","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":"Alterations in amygdala subregions—Default mode network connectivity after treatment in patients with schizophrenia","authors":"Jianxiong Xu, Jiaquan Liang, Haohao Yan, Chunguo Zhang, Xinglian Zhang, Xuesong Li, Wei Huang, Huagui Guo, Yu Yang, Jinzhong Ye, Yangpan Ou, Wen Deng, Jinbing Xu, Xiaoling Li, Guojun Xie, Wenbin Guo","doi":"10.1002/jnr.25376","DOIUrl":"10.1002/jnr.25376","url":null,"abstract":"<p>Disrupted connectivity in the default mode network (DMN) during resting-state functional MRI (rs-fMRI) is well-documented in schizophrenia (SCZ). The amygdala, a key component in the neurobiology of SCZ, comprises distinct subregions that may exert varying effects on the disorder. This study aimed to investigate variations in functional connectivity (FC) between distinct amygdala subregions and the DMN in SCZ individuals and explore the effects of treatment on these connections. Fifty-six SCZ patients and 51 healthy controls underwent FC analysis and questionnaire surveys during resting state. The amygdala was selected as the region of interest (ROI) and subdivided into four parts. Changes in FC were examined, and correlations between questionnaire scores and brain activity were explored. Pre-treatment, SCZ patients exhibited reduced FC between the amygdala and DMN compared to HCs. After treatment, significant differences persisted in the right medial amygdala, while other regions did not differ significantly from controls. In addition, PANSS scores positively correlated with FC between the Right Medial Amygdala and the left SMFC (<i>r</i> = .347, <i>p</i> = .009), while RBANS5A scores showed a positive correlation with FC between the Left Lateral Amygdala and the right MTG (rho = −.347, <i>p</i> = .009). The rsFC between the amygdala and the DMN plays a crucial role in the treatment mechanisms of SCZ. This could provide a promising predictive indicator for understanding the neural mechanisms behind treatment and symptomatic improvement.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000126","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}
Vanessa Valéria Miron, Charles Elias Assmann, Vitor Bastianello Mostardeiro, Marcylene Vieira da Silveira, Priscila Marquezan Copetti, Bianca Fagan Bissacotti, Adriel Antonio Schirmann, Milagros Fanny Vera Castro, Jessié Martins Gutierres, Marilda da Cruz Fernandes, Fernanda Tibolla Viero, Vera Maria Morsch, Maria Rosa Chitolina Schetinger, Andréia Machado Cardoso
{"title":"Neuroprotective effect of long-term resistance physical exercise against memory damage elicited by a lipopolysaccharide-induced neuroinflammation model in male rats","authors":"Vanessa Valéria Miron, Charles Elias Assmann, Vitor Bastianello Mostardeiro, Marcylene Vieira da Silveira, Priscila Marquezan Copetti, Bianca Fagan Bissacotti, Adriel Antonio Schirmann, Milagros Fanny Vera Castro, Jessié Martins Gutierres, Marilda da Cruz Fernandes, Fernanda Tibolla Viero, Vera Maria Morsch, Maria Rosa Chitolina Schetinger, Andréia Machado Cardoso","doi":"10.1002/jnr.25370","DOIUrl":"10.1002/jnr.25370","url":null,"abstract":"<p>Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000127","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":"EXPRESSION OF CONCERN: Transient expression of fluorescent tau proteins promotes process formation in PC12 cells: Contributions of the tau C-terminus to this process","authors":"","doi":"10.1002/jnr.25374","DOIUrl":"10.1002/jnr.25374","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: J.-Z. Yu, J. Kuret, and M. M. Rasenick, “Transient Expression of Fluorescent Tau Proteins Promotes Process Formation in PC12 Cells: Contributions of the Tau C-terminus to This Process,” <i>Journal of Neuroscience Research</i> 67, no. 5 (2002): 625–633, https://doi.org/10.1002/jnr.10152.</p><p>This Expression of Concern for the above article published online on 16 January 2002, in Wiley Online Library (wileyonlinelibrary.com), has been published by agreement between the journal Editors-in-Chief, Cristina A. Ghiani and J. Paula Warrington; and Wiley Periodicals LLC. The Expression of Concern has been agreed following concerns raised regarding suspected duplication between the two images, Tau23-GFP (72 hours) presented in Figure 4a and Tau 24 (174-383)-GFP (24 hours) presented in Figure 5a. The authors acknowledge the duplication but due to the length of time that has elapsed since the study was conducted and published, they were unable to provide an explanation or the original data. The journal has decided to issue an Expression of Concern to alert the readers.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906862","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":"Early postnatal development of the primary visual areas 17 and 18 of the cat cerebral cortex: An SMI-32 study","authors":"A. A. Mikhalkin, N. I. Nikitina, N. S. Merkulyeva","doi":"10.1002/jnr.25375","DOIUrl":"10.1002/jnr.25375","url":null,"abstract":"<p>Using anti-neurofilament H non-phosphorylated antibodies (SMI-32) as markers for the neuronal maturation level and Y channel responsible for motion processing, we investigated early postnatal development of the primary visual areas 17 and 18 in cats aged 0, 10, 14, and 34 days and in adults. Two analyzed parameters of SMI-32-immunolabeling were used: the total proportion of SMI-32-labeling and the density of labeled neurons. (i) The developmental time course of the total proportion of SMI-32-labeling shows the general increase in the accumulation of heavy-chain neurofilaments. This parameter showed a different time course for cortical layer development; the maximal increment in the total labeling in layer V occurred between the second and fifth postnatal weeks and in layers II–III and VI after the fifth postnatal week. In addition, the delay in accumulation of SMI-32-labeling was shown in layer V of the area 17 periphery representation during the first two postnatal weeks. (ii) The density of SMI-32-labeled neurons decreased in all layers of area 18, but was increased, decreased, or had a transient peak in layers II–III, V, and VI of area 17, respectively. The transient peak is in good correspondence with some transient neurochemical features previously revealed for different classes of cortical and thalamic neurons and reflects the time course of the early development of the thalamocortical circuitry. Some similarities between the time courses for the development of SMI-32-labeling in areas 17/18 and in A- and C-laminae of the LGNd allow us to propose heterochronous postnatal development of two Y sub-channels.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893614","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}
Fernando Osuna-Lopez, J. Manuel Herrera-Zamora, Miriam E. Reyes-Méndez, Raúl A. Aguilar-Roblero, Enrique A. Sánchez-Pastor, Ricardo A. Navarro-Polanco, Eloy G. Moreno-Galindo, Javier Alamilla
{"title":"Age-, region-, and day/night-related variation of the chloride reversal potential in the rat suprachiasmatic nucleus","authors":"Fernando Osuna-Lopez, J. Manuel Herrera-Zamora, Miriam E. Reyes-Méndez, Raúl A. Aguilar-Roblero, Enrique A. Sánchez-Pastor, Ricardo A. Navarro-Polanco, Eloy G. Moreno-Galindo, Javier Alamilla","doi":"10.1002/jnr.25373","DOIUrl":"10.1002/jnr.25373","url":null,"abstract":"<p>The master control of mammalian circadian rhythms is the suprachiasmatic nucleus (SCN), which is formed by the ventral and dorsal regions. In SCN neurons, GABA has an important function and even excitatory actions in adulthood. However, the physiological role of this neurotransmitter in the developing SCN is unknown. Here, we recorded GABAergic postsynaptic currents (in the perforated-patch configuration using gramicidin) to determine the chloride reversal potential (E<sub>Cl</sub>) and also assessed the immunological expression of the Na-K-Cl cotransporter 1 (NKCC1) at early ages of the rat (postnatal days (P) 3 to 25), during the day and night, in the two SCN regions. We detected that E<sub>Cl</sub> greatly varied with age and depending on the SCN region and time of day. Broadly speaking, E<sub>Cl</sub> was more hyperpolarized with age, except for the oldest age studied (P20–25) in both day and night in the ventral SCN, where it was less negative. Likewise, E<sub>Cl</sub> was more hyperpolarized in the dorsal SCN both during the day and at night; while E<sub>Cl</sub> was more negative at night both in the ventral and the dorsal SCN. Moreover, the total NKCC1 fluorescent expression was higher during the day than at night. These results imply that NKCC1 regulates the circadian and developmental fluctuations in the [Cl<sup>−</sup>]<sub>i</sub> to fine-tune E<sub>Cl</sub>, which is crucial for either excitatory or inhibitory GABAergic actions to occur in the SCN.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889494","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}
Bei Jing, Zhen-ni Chen, Wai-mei Si, Jia-ji Zhao, Guo-ping Zhao, Di Zhang
{"title":"(+)-Catechin attenuates CCI-induced neuropathic pain in male rats by promoting the Nrf2 antioxidant pathway to inhibit ROS/TLR4/NF-κB-mediated activation of the NLRP3 inflammasome","authors":"Bei Jing, Zhen-ni Chen, Wai-mei Si, Jia-ji Zhao, Guo-ping Zhao, Di Zhang","doi":"10.1002/jnr.25372","DOIUrl":"10.1002/jnr.25372","url":null,"abstract":"<p>The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague–Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1β. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860052","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}