CNS Neuroscience & Therapeutics最新文献

{"title":"Visual cortex repetitive transcranial magnetic stimulation (rTMS) reversing neurodevelopmental impairments in adolescents with major psychiatric disorders (MPDs): A cross-species translational study","authors":"Juan Liu,&nbsp;Huiling Guo,&nbsp;Jingyu Yang,&nbsp;Yao Xiao,&nbsp;Aoling Cai,&nbsp;Tongtong Zhao,&nbsp;Fay Y. Womer,&nbsp;Pengfei Zhao,&nbsp;Junjie Zheng,&nbsp;Xizhe Zhang,&nbsp;Jie Wang,&nbsp;Rongxin Zhu,&nbsp;Fei Wang","doi":"10.1111/cns.14427","DOIUrl":"10.1111/cns.14427","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Neurodevelopmental impairments are closely linked to the basis of adolescent major psychiatric disorders (MPDs). The visual cortex can regulate neuroplasticity throughout the brain during critical periods of neurodevelopment, which may provide a promising target for neuromodulation therapy. This cross-species translational study examined the effects of visual cortex repetitive transcranial magnetic stimulation (rTMS) on neurodevelopmental impairments in MPDs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Visual cortex rTMS was performed in both adolescent methylazoxymethanol acetate (MAM) rats and patients with MPDs. Functional magnetic resonance imaging (fMRI) and brain tissue proteomic data in rats and fMRI and clinical symptom data in patients were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The regional homogeneity (ReHo) analysis of fMRI data revealed an increase in the frontal cortex and a decrease in the posterior cortex in the MAM rats, representing the abnormal neurodevelopmental pattern in MPDs. In regard to the effects of rTMS, similar neuroimaging changes, particularly reduced frontal ReHo, were found both in MAM rats and adolescent patients, suggesting that rTMS may reverse the abnormal neurodevelopmental pattern. Proteomic analysis revealed that rTMS modulated frontal synapse-associated proteins, which may be the underpinnings of rTMS efficacy. Furthermore, a positive relationship was observed between frontal ReHo and clinical symptoms after rTMS in patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Visual cortex rTMS was proven to be an effective treatment for adolescent MPDs, and the underlying neural and molecular mechanisms were uncovered. Our study provides translational evidence for therapeutics targeting the neurodevelopmental factor in MPDs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10280452","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":"Ligustilide-loaded liposome ameliorates mitochondrial impairments and improves cognitive function via the PKA/AKAP1 signaling pathway in a mouse model of Alzheimer's disease","authors":"Qi Zhang,&nbsp;Xiangxiang Zhang,&nbsp;Bing Yang,&nbsp;Yan Li,&nbsp;Xue-Heng Sun,&nbsp;Xiang Li,&nbsp;Ping Sui,&nbsp;Yi-Bin Wang,&nbsp;Shu-Yu Tian,&nbsp;Chun-Yan Wang","doi":"10.1111/cns.14460","DOIUrl":"10.1111/cns.14460","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oxidative stress is an early event in the development of Alzheimer's disease (AD) and maybe a pivotal point of interaction governing AD pathogenesis; oxidative stress contributes to metabolism imbalance, protein misfolding, neuroinflammation and apoptosis. Excess reactive oxygen species (ROS) are a major contributor to oxidative stress. As vital sources of ROS, mitochondria are also the primary targets of ROS attack. Seeking effective avenues to reduce oxidative stress has attracted increasing attention for AD intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We developed liposome-packaged Ligustilide (LIG) and investigated its effects on mitochondrial function and AD-like pathology in the APPswe/PS1dE9 (APP/PS1) mouse model of AD, and analyzed possible mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed that LIG-loaded liposome (LIG-LPs) treatment reduced oxidative stress and β-amyloid (Aβ) deposition and mitigated cognitive impairment in APP/PS1 mice. LIG management alleviated the destruction of the inner structure in the hippocampal mitochondria and ameliorated the imbalance between mitochondrial fission and fusion in the APP/PS1 mouse brain. We showed that the decline in cAMP-dependent protein kinase A (PKA) and A-kinase anchor protein 1 for PKA (AKAP1) was associated with oxidative stress and AD-like pathology. We confirmed that LIG-mediated antioxidant properties and neuroprotection were involved in upregulating the PKA/AKAP1 signaling in APPswe cells in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Liposome packaging for LIG is relatively biosafe and can overcome the instability of LIG. LIG alleviates mitochondrial dysfunctions and cognitive impairment via the PKA/AKAP1 signaling pathway. Our results provide experimental evidence that LIG-LPs may be a promising agent for AD therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286949","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":"Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease","authors":"Chuanxi Tang,&nbsp;Ruiao Sun,&nbsp;Ke Xue,&nbsp;Mengying Wang,&nbsp;Sijie Liang,&nbsp;Piniel Alphayo Kambey,&nbsp;Mingyu Shi,&nbsp;Changyu Wu,&nbsp;Gang Chen,&nbsp;Dianshuai Gao","doi":"10.1111/cns.14461","DOIUrl":"10.1111/cns.14461","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Aberrations in brain connections are implicated in the pathogenesis of Parkinson's disease (PD). We previously demonstrated that Glial cell-derived neurotrophic factor (GDNF) reduction is associated with cognition decline. Nonetheless, it is elusive if the pattern of brain topological connectivity differed across PD with divergent serum GDNF levels, and the accompanying profile of cognitive deficits has yet to be determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected data on the participants' cognition, demographics, and serum GDNF levels. Participants underwent 3.0T magnetic resonance imaging, and we assessed the degree centrality, brain network topology, and cortical thickness of the healthy control (HC) (<i>n</i> = 25), PD-high-GDNF (<i>n</i> = 19), and PD-low-GDNF (<i>n</i> = 19) groups using graph-theoretic measures of resting-state functional MRI to reveal how much brain connectivity varies and its clinical correlates, as well as to determine factors predicting the cognitive status in PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results show different network properties between groups. Degree centrality abnormalities were found in the right inferior frontal gyrus and right parietal lobe postcentral gyrus, linked with cognition scores. The two aberrant clusters serve as a potentially powerful signal for determining whether a patient has PD and the patient's cognition level after integrating with GDNF, duration, and dopamine dosage. Moreover, we found a significant positive relationship between the thickness of the left caudal middle frontal lobe and a plethora of cognitive domains. Further discriminant analysis revealed that the cortical thickness of this region could distinguish PD patients from healthy controls. The mental state evaluation will also be more precise when paired with GDNF and duration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings reveal that the topological features of brain networks and cortical thickness are altered in PD patients with cognitive deficits. The above change, accompanied by the serum GDNF, may have merit as a diagnosis marker for PD and, arguably, cognition status.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10651975","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":"Breakdown of oscillatory effective networks in disorders of consciousness","authors":"Yang Bai,&nbsp;Anjuan Gong,&nbsp;Qijun Wang,&nbsp;Yongkun Guo,&nbsp;Yin Zhang,&nbsp;Zhen Feng","doi":"10.1111/cns.14469","DOIUrl":"10.1111/cns.14469","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Combining transcranial magnetic stimulation with electroencephalography (TMS-EEG), oscillatory reactivity can be measured, allowing us to investigate the interaction between local and distant cortical oscillations. However, the extent to which human consciousness is related to these oscillatory effective networks has yet to be explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We tend to investigate the link between oscillatory effective networks and brain consciousness, by monitoring the global transmission of TMS-induced oscillations in disorders of consciousness (DOC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A cohort of DOC patients was included in this study, which included 28 patients with a minimally conscious state (MCS) and 20 patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Additionally, 25 healthy controls were enrolled. The oscillatory reactivity to single-pulse TMS of the frontal, sensorimotor and parietal cortex was measured using event-related spectral perturbation of TMS-EEG. The temporal–spatial properties of the oscillatory reactivity were illustrated through life time, decay gradients and accumulative power. In DOC patients, an oscillatory reactivity was observed to be temporally and spatially suppressed. TMS-EEG of DOC patients showed that the oscillations did not travel as far in healthy controls, in terms of both temporal and spatial dimensions. Moreover, cortical theta reactivity was found to be a reliable indicator in distinguishing DOC versus healthy controls when TMS of the parietal region and in distinguishing MCS versus VS/UWS when TMS of the frontal region. Additionally, a positive correlation was observed between the Coma Recovery Scale-Revised scores of the DOC patients and the cortical theta reactivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings revealed a breakdown of oscillatory effective networks in DOC patients, which has implications for the use of TMS-EEG in DOC evaluation and offers a neural oscillation viewpoint on the neurological basis of human consciousness.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10339077","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":"Potentiated GABAergic neuronal activities in the basolateral amygdala alleviate stress-induced depressive behaviors","authors":"Muhammad Asim,&nbsp;Huajie Wang,&nbsp;Xi Chen,&nbsp;Jufang He","doi":"10.1111/cns.14422","DOIUrl":"10.1111/cns.14422","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Major depressive disorder is a severe psychiatric disorder that afflicts ~17% of the world population. Neuroimaging investigations of depressed patients have consistently reported the dysfunction of the basolateral amygdala in the pathophysiology of depression. However, how the BLA and related circuits are implicated in the pathogenesis of depression is poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we combined fiber photometry, immediate early gene expression (c-fos), optogenetics, chemogenetics, behavioral analysis, and viral tracing techniques to provide multiple lines of evidence of how the BLA neurons mediate depressive-like behavior.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrated that the aversive stimuli elevated the neuronal activity of the excitatory BLA neurons (BLA^CAMKII neurons). Optogenetic activation of CAMKII neurons facilitates the induction of depressive-like behavior while inhibition of these neurons alleviates the depressive-like behavior. Next, we found that the chemogenetic inhibition of GABAergic neurons in the BLA (BLA^GABA) increased the firing frequency of CAMKII neurons and mediates the depressive-like phenotypes. Finally, through fiber photometry recording and chemogenetic manipulation, we proved that the activation of BLA^GABA neurons inhibits BLA^CAMKII neuronal activity and alleviates depressive-like behavior in the mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thus, through evaluating BLA^GABA and BLA^CAMKII neurons by distinct interaction, the BLA regulates depressive-like behavior.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628065","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":"The cell-specific roles of Nrf2 in acute and chronic phases of ischemic stroke","authors":"George Fadoul,&nbsp;Milos Ikonomovic,&nbsp;Feng Zhang,&nbsp;Tuo Yang","doi":"10.1111/cns.14462","DOIUrl":"10.1111/cns.14462","url":null,"abstract":"<p>Ischemic stroke refers to the sudden loss of blood flow in a specific area of the brain. It is the fifth leading cause of mortality and the leading cause of permanent disability. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) controls the production of several antioxidants and protective proteins and it has been investigated as a possible pharmaceutical target for reducing harmful oxidative events in brain ischemia. Each cell type exhibits different roles and behaviors in different phases post-stroke, which is comprehensive yet important to understand to optimize management strategies and goals for care for stroke patients. In this review, we comprehensively summarize the protective effects of Nrf2 in experimental ischemic stroke, emphasizing the role of Nrf2 in different cell types including neurons, astrocytes, oligodendrocytes, microglia, and endothelial cells during acute and chronic phases of stroke and providing insights on the neuroprotective role of Nrf2 on each cell type throughout the long term of stroke care. We also highlight the importance of targeting Nrf2 in clinical settings while considering a variety of important factors such as age, drug dosage, delivery route, and time of administration.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628058","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":"Postoperative use of steroids for peri-electrode edema after deep brain stimulation surgery: A retrospective cohort study","authors":"Bin Wu,&nbsp;Yuting Ling,&nbsp;Changming Zhang,&nbsp;Jiakun Xu,&nbsp;Chao Yang,&nbsp;Nan Jiang,&nbsp;Ling Chen,&nbsp;Jinlong Liu","doi":"10.1111/cns.14470","DOIUrl":"10.1111/cns.14470","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To review the incidence and extent of peri-electrode edema after DBS and to clarify the effect of postoperative use of steroids on the peri-electrode edema.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cohort study included 250 patients who underwent bilateral subthalamic nucleus (STN) DBS surgery with intact MRI within 1 month after DBS surgery. Patients were divided into steroid and non-steroid groups, based on postoperative steroids use. The occurrence and extent of peri-electrode edema were compared between the two groups, and other associated factors were analyzed using univariate and multivariate methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Peri-electrode edema &gt;1 cm³ in at least one hemisphere was reported in 215 (86.00%) patients. The mean volume of peri-electrode edema observed in the steroid group was significantly smaller than in the non-steroid group (8.09 ± 8.47 cm³ vs 17.10 ± 16.90 cm³, <i>p</i> &lt; 0.001). In the steroid group, 104 (32.91%) of the 316 implanted electrodes present with edema less than 1 cm³, whereas in the non-steroid group, only 27 (14.67%) of the 184 implanted electrodes present with edema less than 1 cm³ (<i>p</i> &lt; 0.001). Multivariate analysis indicated that lesser peri-electrode edema was significantly associated with postoperative steroids use and general anesthesia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Peri-electrode edema is common after DBS surgery, and postoperative steroids use reduces the occurrence and extent of peri-electrode edema.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10610959","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":"Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats","authors":"Xiaofeng Wu,&nbsp;Hanfang Xu,&nbsp;Ningxi Zeng,&nbsp;Huizhen Li,&nbsp;Gaolei Yao,&nbsp;Kaige Liu,&nbsp;Can Yan,&nbsp;Lili Wu","doi":"10.1111/cns.14455","DOIUrl":"10.1111/cns.14455","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Late-onset depression (LOD) is defined as primary depression that first manifests after the age of 65. Luteolin (LUT) is a natural flavonoid that has shown promising antidepressant effects and improvement in neurological function in previous studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>In this study, we utilized UPLC–MS/MS non-targeted metabolomics techniques, along with molecular docking technology and experimental validation, to explore the mechanism of LUT in treating LOD from a metabolomics perspective.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The behavioral results of our study demonstrate that LUT significantly ameliorated anxiety and depression-like behaviors while enhancing cognitive function in LOD rats. Metabolomic analysis revealed that the effects of LUT on LOD rats were primarily mediated through the glycerophospholipid metabolic pathway in the hippocampus and prefrontal cortex. The levels of key lipid metabolites, phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), in the glycerophospholipid metabolic pathway were significantly altered by LUT treatment, with PC and PE showing significant correlations with behavioral indices. Molecular docking analysis indicated that LUT had strong binding activity with phosphatidylserine synthase 1 (PTDSS1), phosphatidylserine synthase 2 (PTDSS2), and phosphatidylserine decarboxylase (PISD), which are involved in the transformation and synthesis of PC, PE, and PS. Lastly, our study explored the reasons for the opposing trends of PC, PE, and PS in the hippocampus and prefrontal cortex from the perspective of autophagy, which may be attributable to the bidirectional regulation of autophagy in distinct brain regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results revealed significant alterations in the glycerophospholipid metabolism pathways in both the hippocampus and prefrontal cortex of LOD rats. Moreover, LUT appears to regulate autophagy disorders by specifically modulating glycerophospholipid metabolism in different brain regions of LOD rats, consequently alleviating depression-like behavior in these animals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10610966","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":"CD8+ T cell infiltration and proliferation in the brainstem during experimental cerebral malaria","authors":"Jun Wang,&nbsp;Qinghao Zhu,&nbsp;Yan Shen,&nbsp;Jiao Liang,&nbsp;Yi Wang,&nbsp;Yuxiao Huang,&nbsp;Guodong Tong,&nbsp;Xu Wang,&nbsp;Ningning Zhang,&nbsp;Kangjie Yu,&nbsp;Yinghui Li,&nbsp;Ya Zhao","doi":"10.1111/cns.14431","DOIUrl":"10.1111/cns.14431","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Cerebral malaria (CM) is a lethal neuroinflammatory disease caused by <i>Plasmodium</i> infection. Immune cells and brain parenchyma cells contribute to the pathogenesis of CM. However, a systematic examination of the changes that occur in the brain parenchyma region during CM at the single-cell resolution is still poorly studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore cell composition and CD8⁺ T cell infiltration, single-cell RNA sequencing (scRNA-seq) was performed on the brainstems of healthy and experimental cerebral malaria (ECM) mice. Then CD8⁺ T cell infiltration was confirmed by flow cytometry and immunofluorescence assays. Subsequently, the characteristics of the brain-infiltrated CD8⁺ T cells were analyzed. Finally, the interactions between parenchyma cells and brain-infiltrated CD8⁺ T cells were studied with an astrocytes-CD8⁺ T cell cocultured model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The brainstem is the most severely damaged site during ECM. ScRNA-seq revealed a large number of CD8⁺ T cells infiltrating into the brainstem in ECM mice. Brain-infiltrated CD8⁺ T cells were highly activated according to scRNA-seq, immunofluorescence, and flow cytometry assays. Further analysis found a subset of ki-67⁺ CD8⁺ T cells that have a higher transcriptional level of genes related to T cell function, activation, and proliferation, suggesting that they were exposed to specific antigens presented by brain parenchyma cells. Brain-infiltrated CD8⁺ T cells were the only prominent source of IFN-γ in this single-cell analysis. Astrocytes, which have a high interferon response, act as cross-presenting cells to recruit and re-activate brain-infiltrated CD8⁺ T cells. We also found that brain-infiltrated CD8⁺ T cells were highly expressed immune checkpoint molecule PD-1, while parenchyma cells showed up-regulation of PD-L1 after infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings reveal a novel interaction between brain-infiltrated CD8⁺ T cells and parenchyma cells in the ECM brainstem, suggesting that the PD-1/PD-L1 signal pathway is a promising adjunctive therapeutic strategy for ECM targeting over-activated CD8⁺ T cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10580429","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":"Human umbilical cord mesenchymal stem cell-derived exosomes attenuate neuroinflammation and oxidative stress through the NRF2/NF-κB/NLRP3 pathway","authors":"Ji Che,&nbsp;Hui Wang,&nbsp;Jing Dong,&nbsp;Yuanyuan Wu,&nbsp;Haichao Zhang,&nbsp;Lei Fu,&nbsp;Jun Zhang","doi":"10.1111/cns.14454","DOIUrl":"10.1111/cns.14454","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We investigated whether human umbilical cord mesenchymal stem cell (hUC-MSC)-derived exosomes bear therapeutic potential against lipopolysaccharide (LPS)-induced neuroinflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Exosomes were isolated from hUC-MSC supernatant by ultra-high-speed centrifugation and characterized by transmission electron microscopy and western blotting. Inflammatory responses were induced by LPS in BV-2 cells, primary microglial cultures, and C57BL/6J mice. H₂O₂ was also used to induce inflammation and oxidative stress in BV-2 cells. The effects of hUC-MSC-derived exosomes on inflammatory cytokine expression, oxidative stress, and microglia polarization were studied by immunofluorescence and western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with hUC-MSC-derived exosomes significantly decreased the LPS- or H₂O₂-induced oxidative stress and expression of pro-inflammatory cytokines (IL-6 and TNF-α) in vitro, while promoting an anti-inflammatory (classical M2) phenotype in an LPS-treated mouse model. Mechanistically, the exosomes increased the NRF2 levels and inhibited the LPS-induced NF-κB p65 phosphorylation and NLRP3 inflammasome activation. In contrast, the reactive oxygen species scavenger NAC and NF-κB inhibitor BAY 11–7082 also inhibited the LPS-induced NLRP3 inflammasome activation and switched to the classical M2 phenotype. Treatment with the NRF2 inhibitor ML385 abolished the anti-inflammatory and anti-oxidative effects of the exosomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>hUC-MSC-derived exosomes ameliorated LPS/H₂O₂-induced neuroinflammation and oxidative stress by inhibiting the microglial NRF2/NF-κB/NLRP3 signaling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 3","pages":""},"PeriodicalIF":5.5,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268332","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}