CNS Neuroscience & Therapeutics最新文献

{"title":"Endothelial Changes at Different Stages After Ischemic Stroke Contribute to the Regulation of Immune Cell Infiltration","authors":"Xuejiao Dai,&nbsp;Xiaotao Zhang,&nbsp;Jiarui Chen,&nbsp;Qia Zhang,&nbsp;Huaming Li,&nbsp;An Ping,&nbsp;Yuchen Liu,&nbsp;Jingyi Zhou,&nbsp;Jianmin Zhang,&nbsp;Ligen Shi,&nbsp;Jianan Lu","doi":"10.1111/cns.70456","DOIUrl":"https://doi.org/10.1111/cns.70456","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Following ischemic stroke, peripheral immune cell infiltration is characterized by myeloid cell predominance in the acute phase and lymphoid cell infiltration in the subacute to chronic phases. Endothelial cells, as a critical interface between the peripheral circulation and the brain, upregulate adhesion molecules to facilitate immune cell infiltration. However, it remains unclear whether endothelial cells exhibit functional differences at different stages after ischemic stroke and how these differences affect immune cell infiltration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed single-cell RNA sequencing on peripheral immune and endothelial cells from Sham and middle cerebral artery occlusion (MCAO) mice at 3 and 14 days post-MCAO. Subsequent analysis of the sequencing data, combined with flow cytometry and immunofluorescence staining, was used to investigate the relationship between endothelial cell changes at different stages of stroke and immune cell infiltration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed that the infiltration capacity of peripheral immune cells did not significantly increase at different stages after MCAO. However, endothelial cells underwent significant changes. By Day 3 post-MCAO, there was an increased proportion of venous endothelial cells with enhanced angiogenesis and adhesion functions. In this acute phase, newly formed venous endothelial cells with high expression of the adhesion molecule ICAM-1 were observed, promoting the infiltration of myeloid cells and NKT cells. From the acute to chronic phases, endothelial angiogenesis gradually decreased, accompanied by a marked increase in antigen presentation function. At 14 days post-MCAO, an increased proportion of VCAM-1-expressing venous endothelial cells was observed, potentially facilitating the infiltration of T cells and a subset of neutrophils. Furthermore, we discovered that the differential changes in venous endothelial cells at different stages after MCAO may be driven by distinct differentiation and proliferation patterns regulated by different signaling pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study highlights that the differential expression of adhesion molecules and functional changes in endothelial cells at distinct stages after ischemic stroke may regulate the infiltration patterns of peripheral immune cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Glucose Metabolism Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Longitudinal Study From SILCODE","authors":"Min Wei,&nbsp;Luyao Wang,&nbsp;Xianfeng Yu,&nbsp;Wenjing Hu,&nbsp;Min Wang,&nbsp;Qi Zhang,&nbsp;Tengfei Guo,&nbsp;Jiayi Zhong,&nbsp;Chenyang Li,&nbsp;Jiehui Jiang,&nbsp;Ying Han","doi":"10.1111/cns.70264","DOIUrl":"https://doi.org/10.1111/cns.70264","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Glucose metabolism and plasma biomarkers have emerged as important early markers in Alzheimer's disease. Different subtypes (single memory domain, multidomain) of subjective cognitive decline (SCD) may represent distinct stages of disease progression, but the differences in glucose metabolism remain unclear. This study focused on exploring the differences in glucose metabolism between different SCD subtypes and the correlation with plasma biomarkers based on &lt;sup&gt;18&lt;/sup&gt;F-FDG PET.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this study, thirty-three normal controls (NCs), thirty-five individuals with single memory domain SCD (sd-SCD), thirty-nine individuals with multidomain SCD (md-SCD), and twenty-one cognitively impaired (CI) individuals were involved. We investigated the standardized uptake value ratio (SUVR) and voxel differences between the sd-SCD and md-SCD groups followed by FDR and GRF corrections, with an average follow-up time of 44.98 ± 16.49 months. Correlation analyses were employed to assess relationships between FDG-PET SUVR and neuropsychological scales as well as plasma biomarkers. Finally, Kaplan–Meier survival analysis was used to investigate the risk of cognitive decline conversion among SCD subgroups.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;After controlling for the effects of covariates, the following brain regions showed voxel differences and lower SUVR in md-SCD groups, including right anterior cingulate and paracingulate gyri (ACG.R, &lt;i&gt;p =&lt;/i&gt; 0.003), left anterior cingulate and paracingulate gyri (ACG.L, &lt;i&gt;p =&lt;/i&gt; 0.003), right middle temporal gyrus (MTG.R, &lt;i&gt;p =&lt;/i&gt; 0.004), and right inferior temporal gyrus (ITG.R, &lt;i&gt;p =&lt;/i&gt; 0.001), compared to the sd-SCD group. SUVR of ACG.R was correlated with plasma Aβ42/40 (&lt;i&gt;r&lt;/i&gt; = 0.435, &lt;i&gt;p&lt;/i&gt; = 0.006) and AVLT-N7 score (&lt;i&gt;r&lt;/i&gt; = 0.347, &lt;i&gt;p&lt;/i&gt; = 0.031) in the md-SCD group while none of the correlations existed in the sd-SCD group. SUVR of MTG.R was also correlated with the AVLT-N7 score (&lt;i&gt;r&lt;/i&gt; = 0.246, &lt;i&gt;p&lt;/i&gt; = 0.035) across SCD individuals. The SCD individuals with positive plasma Aβ42/40, p-tau181, and glucose metabolism in above four regions, or those in the md-SCD group showed an elevated risk of cognitive conversion in comparison to the controls.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Differences in glucose metabolism could be observed between the md-SCD and sd-SCD groups. SCD participants in the md-SCD group, or those with positive biomarkers, might represent a higher risk of cognitive decline con","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SFXN1 Reduction Alleviates Cerebral Ischemia–Reperfusion Injury by Promoting Neuronal Survival and Reducing Neuroinflammation","authors":"Xiangyu Xu,&nbsp;Zhongying Duan,&nbsp;Xin Zhou,&nbsp;Rui Zhao,&nbsp;Jing Xu,&nbsp;Zhaolong Zhang,&nbsp;Mengfei Lv,&nbsp;Qi Wan,&nbsp;Yu Cui","doi":"10.1111/cns.70457","DOIUrl":"https://doi.org/10.1111/cns.70457","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Sideroflexin 1 (SFXN1) is an important inner mitochondrial membrane protein that regulates many physiological and pathological events. However, the role of SFXN1 in cerebral ischemia–reperfusion (I/R)-induced neuronal death remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed in vivo injury models of transient middle cerebral artery occlusion (tMCAO) and in vitro models of lipopolysaccharide (LPS) stimulation and oxygen–glucose deprivation/reperfusion (OGD/R) to investigate the regulatory effects of SFXN1 on neuroinflammation and brain injury. Western blotting, immunofluorescence, and real-time quantitative PCR were utilized to assess SFXN1 expression, proinflammatory signaling pathways activation, and cytokine levels in vitro. Cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Nissl staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SFXN1 expression was upregulated following cerebral I/R injury. Both neurons and microglia exhibited increased SFXN1 expression after oxygen–glucose deprivation/reoxygenation (OGD/R) treatment. SFXN1 knockdown reduced OGD/R-induced neuronal death and alleviated cerebral I/R injury. Additionally, conditioned medium from SFXN1-knockdown microglia reduced neurotoxicity in vitro. Mechanistically, SFXN1 induced mitochondrial dysfunction and neuronal death after OGD/R in an iron-independent manner. Furthermore, SFXN1 promoted the production of proinflammatory cytokines by promoting NF-κB activation, partially through iron transport in microglia after OGD/R.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study reveals the novel role of SFXN1 in exacerbating cerebral I/R injury by reducing neuronal survival through the modulation of mitochondrial function and promotion of microglia-mediated neuroinflammation via NF-κB activation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Duloxetine Supplemented With Pregabalin and Amitriptyline Supplemented With Pregabalin for the Treatment of Postherpetic Neuralgia: A Double-Blind, Randomized Crossover Trial","authors":"Yue Wang,&nbsp;Chenchen Wu,&nbsp;Yanan Liu,&nbsp;Youpan Lou,&nbsp;Cheng Chen,&nbsp;Qianqian Chen,&nbsp;Xihan Li,&nbsp;Chao Ma,&nbsp;Jing Li,&nbsp;Ying Huang","doi":"10.1111/cns.70460","DOIUrl":"https://doi.org/10.1111/cns.70460","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ), and current treatment regimens often fail to effectively control the pain.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aim&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The purpose of this study is to compare the efficacy and tolerability of duloxetine combined with pregabalin and amitriptyline combined with pregabalin in the treatment of PHN, as well as their impact on sleep and quality of life in patients with PHN.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This is a double-blind, randomized, crossover trial involving PHN patients. About 220 participants were randomly assigned (1:1) to either the duloxetine combined with pregabalin or the amitriptyline combined with pregabalin. The patient takes duloxetine or amitriptyline orally before bedtime for 6 weeks each time. Perform a 2-week single-blind placebo washout between the two treatments, and a 2-week single-blind placebo washout at the end of the treatment period. In the last week of the treatment cycle, evaluate the 7-day average daily pain, Pittsburgh Sleep Quality Index, 17-item Hamilton Depression Rating Scale, 36-Item Short Form Health Survey, and record the occurrence of major adverse events. A median reduction of 50%, 25%–50%, and 25% in pain score is considered good, moderate, and mild improvement, respectively.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Both treatment methods can significantly improve the baseline pain value (&lt;i&gt;p&lt;/i&gt; &lt; 0.001 for both). The combination of duloxetine and pregabalin resulted in good, moderate, and mild pain relief of 52%, 24%, and 7%, respectively. The combination of amitriptyline and pregabalin resulted in good, moderate, and mild pain relief of 48%, 21%, and 9%, respectively. There was no significant difference in the measurement of various results between the two groups. In the reported adverse events, patients in the amitriptyline group had significantly more dry mouth compared to the duloxetine group (26% vs. 11%; &lt;i&gt;p&lt;/i&gt; = 0.008).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Duloxetine and amitriptyline have similar analgesic effects, and the difference is not statistically significant. The combination of pregabalin has good tolerability and better pain relief in PHN patients, thus providing clinically relevant benefits.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;&lt;b&gt;Trial Registration:&lt;/b&gt; Chinese Clinical Trial Registry: ChiCTR2100054831&lt;/p&gt;\u0000 &lt;/","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of NA-1 on Pericyte-Driven Vasoconstriction and Its Role in No-Reflow During Cerebral Ischemia–Reperfusion","authors":"Xinxuan Yang,&nbsp;Jiahui Zhao,&nbsp;Hao Tian,&nbsp;Ximing Nie,&nbsp;Lina Zheng,&nbsp;Xin Liu,&nbsp;Zheng Z. Wei,&nbsp;Yuchuan Ding,&nbsp;Liping Liu","doi":"10.1111/cns.70409","DOIUrl":"https://doi.org/10.1111/cns.70409","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The no-reflow phenomenon in the ischemic brain following arterial recanalization leads to poor prognosis. Previous studies suggest that the clinically proven NA-1 drug, with disruption of PSD95 in the neuronal terminals alongside the cerebral microvasculature, may inhibit pericytic contraction of microvessels by reducing endothelin-1 secretion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A 1.5-h tMCAO model using Balb/c mice was employed. In vivo two-photon imaging and immunofluorescence staining were employed to assess the constriction effect of pericytes on capillaries. The impact of NR2B9c/NA-1 administration (intravenously infused at a dose of 10 μmol/kg) on pericyte constriction was evaluated through immunofluorescent staining of brain sections. Additionally, The effect of NA-1 on cerebral perfusion was assessed using laser speckle blood flow monitoring, whole brain slice perfusion, and high-magnification capillary imaging. Enzyme-linked immunosorbent Assay (ELISA) was conducted to determine changes in quantitative ONOO⁻ and endothelin-1 (ET-1) content after tat-NA-1 administration. Lastly, microtubule-associated protein 2 (MAP2) staining and behavioral scores were used to evaluate the effects of NA-1 on infarct size and behavioral deficits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vivo two-photon imaging and immunofluorescence staining revealed that pericyte constriction following ischemia and recanalization resulted in a decreased diameter of capillaries, particularly at the soma and adjacent areas. Notably, capillary obstruction was localized near pericytes. After administration of NA-1, the immunofluorescence staining section showed that the diameter of capillaries at pericytes' soma and in the adjacent parts increased. The ELISA results indicated a reduction in ONOO⁻ and ET-1 levels. Additionally, MAP2 staining revealed a decrease in infarct size, while behavioral scores showed improvements in deficits. This effect of NA-1 was counteracted notably when added ET-1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NA-1 inhibits pericyte constriction following ischemia–reperfusion by reducing ET-1 levels. It improves capillary no-reflow in mice, enhances cerebral perfusion, decreases infarct size, and mitigates behavioral deficits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NDUFA10-Mediated ATP Reduction in Medial Prefrontal Cortex Exacerbates Burst Suppression in Aged Mice","authors":"Huiwen Zhang,&nbsp;Panpan Fang,&nbsp;Gaolin Qiu,&nbsp;Dijia Wang,&nbsp;Jiqian Zhang,&nbsp;Zhilai Yang,&nbsp;Hu Liu,&nbsp;Qiying Shen,&nbsp;Xuesheng Liu","doi":"10.1111/cns.70453","DOIUrl":"https://doi.org/10.1111/cns.70453","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Aging is associated with increased responsiveness to anesthesia-induced burst suppression, which correlates with postoperative cognitive dysfunction and delirium. This study aims to investigate whether the enhanced burst suppression in aged mice under anesthesia is associated with a reduction in ATP levels within the medial prefrontal cortex (mPFC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>EEG recordings were conducted to analyze the burst suppression, and in vivo fiber-optic recording techniques were employed to monitor fluctuations in ATP levels within the mPFC during sevoflurane anesthesia. To elucidate the underlying mechanisms contributing to the observed variations in ATP levels in aged mice, mRNA sequencing was performed. Furthermore, site-specific viral knockdown strategies were implemented to validate the mechanisms of action of key molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed that sevoflurane anesthesia resulted in an increased burst suppression ratio, extended EEG suppression time, and reduced ATP levels in aged mice. Administration of ATP mitigated the anesthesia-induced increase in EEG suppression time. RNA sequencing revealed that NDUFA10, an energy metabolism-related gene, was down-regulated in aged mice. Knockdown of NDUFA10 in mPFC increased burst suppression, whereas the administration of ATP attenuated these changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NDUFA10-driven ATP depletion in the mPFC prolongs sevoflurane-induced burst suppression in aged mice, implicating energy metabolism regulation as a strategy to optimize geriatric anesthesia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases","authors":"Yiwei Zhang,&nbsp;Xiuqin Rao,&nbsp;Jiayi Wang,&nbsp;Hantian Liu,&nbsp;Qixian Wang,&nbsp;Xifeng Wang,&nbsp;Fuzhou Hua,&nbsp;Xilong Guan,&nbsp;Yue Lin","doi":"10.1111/cns.70378","DOIUrl":"https://doi.org/10.1111/cns.70378","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurodegenerative diseases pose significant health challenges in the 21st century, with increasing morbidity and mortality, particularly among the elderly population. One of the key factors contributing to the pathogenesis of these diseases is the disrupted crosstalk between mitochondria and the endoplasmic reticulum. Mitochondria-associated membranes (MAMs), which are regions where the ER interfaces with mitochondria, serve as crucial platforms facilitating communication between these organelles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This review focuses on the structural composition and functions of MAMs and highlights their roles. Additionally, in this review, we summarize the relationship between MAM dysfunction and various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and others. The involvement of key proteins such as Sig-1R, IP3R, and VAPB in maintaining ER-mitochondrial communication and their dysfunction in neurodegenerative diseases is emphasized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Through analyzing the effects of MAM on neurodegenerative diseases, we provide the newest insights and potential therapeutic targets for the treatment of these debilitating conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"11,12-Diacetyl-Carnosol Ameliorates Depression-Like Behaviors and Memory Dysfunction in CUMS Mouse Model via Inhibiting HMGB1-Mediated Neuroinflammation","authors":"Kunying Zhao,&nbsp;Lirong Xiang,&nbsp;Shuda Yang,&nbsp;Xinglong Chen,&nbsp;Xiaomi Yang,&nbsp;Junfang Dong,&nbsp;Shangpeng Wu,&nbsp;Si Yang,&nbsp;Min Zhang,&nbsp;Weiyan Hu","doi":"10.1111/cns.70406","DOIUrl":"https://doi.org/10.1111/cns.70406","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>11,12-Diacetyl-carnosol (DACA), a derivative of carnosol, exhibits significant anti-inflammatory and antioxidant properties. However, its antidepressant effects and underlying mechanisms remain unclear. High mobility group box 1 protein (HMGB1)-mediated inflammatory responses and associated neurofunctional impairments play a crucial role in the pathogenesis of depression. This study aimed to investigate whether DACA exerts anti-inflammatory and antidepressant effects and whether its mechanisms involve the HMGB1/NF-κB/NLRP3 signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>(1) A depression model was established in mice through 6 weeks of chronic unpredictable mild stress (CUMS). From the 4th week of stimulation, the treatment group received DACA for 3 weeks. (2) BV2 cells were stimulated with LPS+ATP, and the treatment group was cultured in DACA medium for 24 h. (3) Supernatants from BV2 cells were used to culture primary neurons. To confirm the critical role of HMGB1 in DACA's antidepressant effects, CUMS-stressed mice were treated with glycyrrhizin (GZA) or the DACA+GZA combination. Depressive-like behaviors were evaluated using the sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), forced swim test (FST), and Morris water maze (MWM). Hippocampal microglial cell and primary neuron morphology were assessed by immunofluorescence, and dendritic spine density in hippocampal neurons was examined using Golgi staining. IL-6 and TNF-α concentrations in mouse serum and BV2 supernatant were measured by ELISA. Western blotting was used to detect protein expressions of HMGB1, NF-κB p65, p-NF-κB p65, NLRP3, and IL-1β in the hippocampus and BV2 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CUMS-exposed mice showed decreased sucrose preference, increased immobility in TST and FST, prolonged escape latency in MWM, and reduced crossings. Microglial activation and upregulation of HMGB1, NF-κB p65, p-NF-κB p65, NLRP3, and IL-1β were observed in both CUMS-stressed mice and LPS+ATP-induced BV2 cells, with reduced dendritic spine density in the hippocampus. DACA significantly reversed these phenomena. The effects of DACA were comparable to those of GZA treatment, and no changes were observed with the DACA+GZA combination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The HMGB1/NF-κB/NLRP3 signaling pathway is involved in DACA's therapeutic effects on depression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70406","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligustrazine Alleviates Blood–Brain Barrier Damage by Downregulating Expression of miR-297c-5p","authors":"Shaoyu Guan,&nbsp;Ruichen Jiang,&nbsp;Xudong Wang,&nbsp;Tong Chen,&nbsp;Ping Yi,&nbsp;Tian Li,&nbsp;Teng Ma,&nbsp;Fang Wang","doi":"10.1111/cns.70367","DOIUrl":"https://doi.org/10.1111/cns.70367","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Ligustrazine (LSZ), an ingredient of <i>Ligusticum chuanxiong</i>, has long been used to treat neurovascular diseases in China. This study investigates its protective effects for the impairment of the blood–brain barrier (BBB) and the underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, the impacts of LSZ on the BBB function were firstly assessed in b. End3 cells in vitro. Oxygen–glucose deprivation (OGD) served as an injury factor and western blot (WB) analyzed the expressions of occludin and ZO-1, two tight junction proteins (TJs), essential for maintaining the integrity of the BBB. After bioinformatics analysis of the transcriptome in vivo, qRT-PCR of miR-297c-5p was conducted and a dual-luciferase reporter assay was used to verify the target protein, occludin, which was confirmed by hippocampal insertion using guide cannulas and microinfection of RNA oligos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A 3-h deprivation of OGD of b. End3 cells resulted in noticeable reductions in the level of occludin and ZO-1. However, administration of LSZ (0.1 μM) effectively restored these decreases. In normal mice, administration of LSZ (25 mg/kg, i.p., once daily for 9 days) resulted in a notable reduction in miR-297c-5p. In the middle cerebral artery occlusion (MCAO) mouse model, increased miR-297c-5p was also reversed by LSZ administration. Bioinformatics analysis revealed one of the targets of miR-297c-5p includes occludin. MiR-297c-5p was found to directly target occludin in the dual-luciferase reporter assay. Transfection of miR-297c-5p agomir into b. End3 cells resulted in a significant reduction in the level of occludin, while transfection of antagomir led to an increase in occludin. Besides, stereotaxic injection of AAV-miR-297c-5p into the hippocampus reduced occludin level in vivo. Ultimately, hippocampal microinfection of RNA oligos provided a confirmation that miR-297c-5p was downregulated by LSZ in MCAO mice with up-regulated occludin expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, the present findings provide new insights into regulating occludin by LSZ through downregulation of miR-297c-5p.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly-IC Alleviates Nitroglycerin-Induced Migraine by Inhibiting Neuroinflammation via TLR3/TRIF Signaling Pathway","authors":"Ye Hong,&nbsp;Mengmeng Ma,&nbsp;Changling Li,&nbsp;Yang Zhang,&nbsp;Yanbo Li,&nbsp;Ning Chen,&nbsp;Jinghuan Fang,&nbsp;Li He","doi":"10.1111/cns.70444","DOIUrl":"https://doi.org/10.1111/cns.70444","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Toll-like receptors (TLRs) play critical roles in pain modulation and immune responses. Polyinosinic-polycytidylic acid (Poly-IC), a TLR3-specific ligand, has shown promise in exerting neuroprotective effects, as it mitigates inflammation in several diseases. Considering that sterile neurogenic inflammation is involved in the pathogenesis of migraine, we explored the impact of Poly-IC on episodic migraine treatment and the potential mechanisms involved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Episodic migraine was induced in male rats via a single intraperitoneal injection of nitroglycerin. Poly-IC (with or without a TLR3 inhibitor) treatment was performed before migraine induction. Pain was assessed according to the mechanical sensitivity threshold, head-directed grooming, and the Rat Grimace Scale. The expression of TLR3 and its downstream molecule TRIF was subsequently examined, after which calcitonin gene-related peptide (CGRP), c-fos, and proinflammatory cytokine expression was assessed. Moreover, TRIF expression in primary cultured neurons was knocked down by shRNA in vitro to further explore the mechanisms by which Poly-IC mediates migraine-like inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Poly-IC treatment significantly upregulated TLR3/TRIF expression, reduced the production of CGRP, c-fos, and inflammatory cytokines, and alleviated allodynia in an animal model of migraine. Moreover, TRIF knockdown blunted the anti-inflammatory effects of Poly-IC treatment in primary cultured neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Poly-IC exerts therapeutic effects against neurogenic inflammation via the TLR3/TRIF signaling pathway in an episodic migraine model.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}