CNS Neuroscience & Therapeutics最新文献

{"title":"Neural Oscillations in the Somatosensory and Motor Cortex Distinguish Dexmedetomidine-Induced Anesthesia and Sleep in Rats","authors":"Dengyun Ge,&nbsp;Chuanliang Han,&nbsp;Chang Liu,&nbsp;Zhiqiang Meng","doi":"10.1111/cns.70262","DOIUrl":"https://doi.org/10.1111/cns.70262","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anesthesia is featured by behavioral and physiological characteristics such as decreased sensory and motor function, loss of consciousness, etc. Some anesthetics such as dexmedetomidine (DEX), induce electroencephalogram signatures close to non-rapid eye movement sleep. Studies have shown that sleep is primarily driven by the activation of subcortical sleep-promoting neural pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>However, the neuronal level electrophysiology features of anesthesia and how they differ from sleep is still not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In the present study, we recorded neuronal activity simultaneously from somatosensory cortex (S1) and motor cortex (M1) during awake, sleep, and DEX-induced anesthesia in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results show that DEX increased local field potential (LFP) power across a relatively wide band (1–25 Hz) in both S1 and M1. The coherence between S1 LFP and M1 LFP increased significantly in the delta and alpha bands. Power spectrum analysis during DEX-induced anesthesia revealed relatively high power in the delta and alpha bands, but low power in the theta and beta bands. Overall, the firing rate of individual neurons decreased after DEX. Correlation analysis of firing rate and LFP power indicate that more neurons were correlated, either positively or negatively, with LFPs during DEX-induced anesthesia compared to sleep.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Although these results showed enhancement of cortical LFP power in both DEX-induced anesthesia and sleep, different patterns of spike-field correlation suggest that the two states may be regulated by different cortical mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Distinguishing anesthesia from sleep with neural oscillations could lead to more personalized, safer, and more effective approaches to managing consciousness in medical settings, with the potential for broad applications in neuroscience and clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431751","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":"Relationships Between Glymphatic System Activity and Tau Burden, Dopaminergic Impairment, Abnormal Glucose Metabolism in Progressive Supranuclear Palsy","authors":"Fangyang Jiao,&nbsp;Qingmin Wang,&nbsp;Jiayi Zhong,&nbsp;Huamei Lin,&nbsp;Jiaying Lu,&nbsp;Luyao Wang,&nbsp;Min Wang,&nbsp;Fengtao Liu,&nbsp;Jiehui Jiang,&nbsp;Chuantao Zuo","doi":"10.1111/cns.70284","DOIUrl":"https://doi.org/10.1111/cns.70284","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by dopaminergic impairment and abnormal glucose metabolism. The glymphatic system can promote the elimination of tau protein. The association between glymphatic function and pathological hallmark in neuroimaging remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Diffusion tensor imaging (DTI) and positron emission tomography (PET) scanning with ¹⁸F-Florzolotau, ¹⁸F-FPCIT, and ¹⁸F-FDG were performed in PSP patients. DTI analysis along the perivascular space (ALPS) index was computed to assess glymphatic function, while the semi-quantitative value was employed to measure tau burden and dopaminergic impairment. The PSP-related pattern (PSPRP) served as an indicator of abnormal metabolic brain network activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PSP patients exhibited changes in ALPS index and tau deposition. ALPS index, tau deposition, and PSPRP expression showed significant correlations with clinical scores. Additionally, ALPS index was correlated with tau deposition and PSPRP expression. However, neither ALPS index nor the clinical scores were correlated with striatum dysfunction. Finally, tau deposition in subcortical regions and PSPRP expression exhibited mediating effects between ALPS index and clinical scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The glymphatic dysfunction is associated with tau deposition and abnormal metabolic brain network activity and is independent of dopaminergic impairment in PSP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431752","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":"NFAT1 Signaling Contributes to Bone Cancer Pain by Regulating IL-18 Expression in Spinal Microglia","authors":"Xuetai Chen,&nbsp;Ying Zeng,&nbsp;Zizhu Wang,&nbsp;Jixiang Zhu,&nbsp;Fengyun Liu,&nbsp;Mingxuan Zhu,&nbsp;Jiayi Zheng,&nbsp;Qingdaiyao Chen,&nbsp;Dongxu Zhai,&nbsp;Yangyang Chen,&nbsp;Jiayao Niu,&nbsp;Zhouya Xue,&nbsp;Guan Sun,&nbsp;Feng Li,&nbsp;Zhiqiang Pan","doi":"10.1111/cns.70222","DOIUrl":"https://doi.org/10.1111/cns.70222","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to test the hypothesis that nuclear factor of activated T cells 1 (NFAT1) signaling contributes to bone cancer pain by regulating interleukin (IL)-18 expression in spinal microglia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study was performed on male mice using a Lewis lung carcinoma-induced bone cancer pain model. Nociceptive behaviors were evaluated by measuring mechanical allodynia, thermal hyperalgesia, and spontaneous pain. Expression levels were measured via real-time quantitative polymerase chain reaction, western blotting, and immunofluorescence analysis. The effect of pharmacologic intervention of spinal NFAT1/IL-18 signaling on bone cancer pain was the primary outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NFAT1 expression was upregulated in the spinal microglia after tumor inoculation. Pharmacological inhibition of NFAT1 upregulation prevented and reversed bone cancer-related pain behaviors. In spinal microglia, NFAT1 inhibition decreased p38 MAPK phosphorylation and IL-18 production. Blocking NFAT1 signaling suppressed tumor-induced neuronal sensitization and microglial activation as well as activation of the N-methyl-D-aspartate receptor and the subsequent Ca²⁺-dependent signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Microglia NFAT1-p38 signaling contributes to bone cancer pain through IL-18-mediated central sensitization in spinal microglia. NFAT1 could be a potential target for therapeutic intervention to prevent bone cancer pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70222","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423914","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":"Astaxanthin Inhibits Ferroptosis of Hippocampal Neurons in Kainic Acid-Induced Epileptic Mice by Activating the Nrf2/GPX4 Signaling Pathway","authors":"Shihao Chen,&nbsp;Linqian Zhao,&nbsp;Xing Jin,&nbsp;Qichang Liu,&nbsp;Yuqing Xiao,&nbsp;Huiqin Xu","doi":"10.1111/cns.70238","DOIUrl":"https://doi.org/10.1111/cns.70238","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epilepsy, a prevalent neurological disorder, is distinguished by episodic abnormal discharges of neurons within the brain, resulting in transient brain dysfunction. Prior research has identified a novel form of cell death termed ferroptosis, which is intricately linked to the initiation and progression of epilepsy. It has been demonstrated that astaxanthin (AST) can inhibit ferroptosis by enhancing the activity of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby providing cytoprotection. Therefore, this study aims to investigate whether AST can alleviate neuronal ferroptosis in epilepsy by activating the Nrf2/GPX4 pathway, thereby exerting a neuroprotective effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By constructing a kainic acid (KA)-induced epilepsy mouse model and a KA-induced HT22 cell model, we employed behavioral testing, Western blot analysis, quantitative real-time reverse transcription qRT-PCR, ferroptosis-related assay kits, immunofluorescence staining, and other methods. These methodologies were utilized to investigate the protective effects and underlying mechanisms of AST on ferroptosis in KA-induced epileptic mice and HT22 neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results demonstrate that AST pretreatment alleviates KA-induced epileptic behaviors and cognitive impairments in mice and mitigates ferroptosis indicators such as lipid peroxidation and mitochondrial morphological alterations. This neuroprotective effect appears to be mediated by the activation of the Nrf2/GPX4 signaling axis. In vitro studies further revealed that AST confers neuroprotection against KA-induced HT22 neuronal cell death, an effect that is abrogated by an Nrf2 inhibitor. Hence, the neuroprotective properties of AST are significantly associated with the modulation of the Nrf2-mediated ferroptosis pathway, as corroborated by bioinformatics analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The AST effectively inhibits neuronal ferroptosis in both in vivo and in vitro epilepsy models via the Nrf2/GPX4 pathway. This finding suggests that AST holds promise as a potential therapeutic agent for the treatment of epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424092","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":"Effects of Pretreatment With Coenzyme Q10 (CoQ10) and High-Intensity Interval Training (HIIT) on FNDC5, Irisin, and BDNF Levels, and Amyloid-Beta (Aβ) Plaque Formation in the Hippocampus of Aβ-Induced Alzheimer's Disease Rats","authors":"Samira Puoyan-Majd,&nbsp;Abdolhossein Parnow,&nbsp;Masome Rashno,&nbsp;Rashid Heidarimoghadam,&nbsp;Alireza komaki","doi":"10.1111/cns.70221","DOIUrl":"https://doi.org/10.1111/cns.70221","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Physical exercise has been shown to protect against cognitive decline in Alzheimer's disease (AD), likely through the upregulation of brain-derived neurotrophic factor (BDNF). Recent studies have reported that exercise activates the FNDC5/irisin pathway in the hippocampus of mice, triggering a neuroprotective gene program that includes BDNF. This study aimed to investigate the effects of 8 weeks of pretreatment with coenzyme Q10 (CoQ10) and high-intensity interval training (HIIT), both individually and in combination, on FNDC5, irisin, BDNF, and amyloid-beta (Aβ) plaque formation in the hippocampus of Aβ-related AD rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, 72 male Wistar rats were randomly assigned to one of the following groups: control, sham, HIIT (low intensity: 3 min running at 50%–60% VO2max; high intensity: 4 min running at 85%–90% VO2max), Q10 (50 mg/kg, orally administered), Q10 + HIIT, AD, AD + HIIT, AD + Q10, and AD + Q10 + HIIT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aβ injection resulted in a trend toward decreased levels of FNDC5, irisin, and BDNF, alongside increased Aβ plaque formation in the hippocampus of Aβ-induced AD rats. However, pretreatment with CoQ10, HIIT, or their combination significantly restored hippocampal levels of FNDC5, irisin, and BDNF, while also inhibiting Aβ plaque accumulation in these rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pretreatment with CoQ10 and HIIT improved the Aβ-induced reduction in BDNF levels probably through the FNDC5/irisin pathway and preventing Aβ plaque formation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424108","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":"Osteopontin in Alzheimer's Disease: A Double-Edged Sword in Neurodegeneration and Neuroprotection—A Systematic Review","authors":"Zahra Azizan,&nbsp;Maryam Bazrgar,&nbsp;Narges Bazgir,&nbsp;Sadra Habibi Moini,&nbsp;Sara Ghaseminejad-Kermani,&nbsp;Kamran Safa,&nbsp;Azam Eshaghian-dorcheh,&nbsp;Mohammad Hossein Harirchian","doi":"10.1111/cns.70269","DOIUrl":"https://doi.org/10.1111/cns.70269","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Osteopontin (OPN) has emerged as a pivotal molecule in Alzheimer's disease (AD), with studies indicating its potential to act as both a neuroprotective agent and a contributor to neurodegeneration. This systematic review aims to elucidate the roles of OPN in AD pathogenesis through inflammatory pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive analysis of current literature on OPN's involvement in AD, focusing on its signaling pathways, cellular interactions, and regulatory mechanisms. We searched PubMed, EMBASE, and Scopus databases by the keyword of Alzheimer's Disease and Osteopontin. Our date search was in 1990 until July 1, 2024 with no language limitation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In a review of 758 studies, a total of 15 reports met the eligibility criteria and were included. Among the findings, four studies provided evidence supporting the protective mechanism of OPN within the context of AD. Eleven studies explain the inflammatory role of OPN. OPN has been shown to play a role in synaptic pruning, microglial activation, and the inflammatory processes associated with AD. Additionally, OPN is implicated in facilitating cellular communication and serves as a chemotactic molecule. It is suggested that the protective effects of OPN are predominantly mediated by the c fragment of the protein and are most prominent in the early stages of AD progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>OPN in AD has dual effects—protecting neurons and contributing to their degeneration. Future research should enhance its protective mechanisms, target specific signaling pathways, and develop therapies to slow AD progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424109","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":"Study on the Mechanisms of Ischemic Stroke Impacting Sleep Homeostasis and Circadian Rhythms in Rats","authors":"Ting-ting Chu,&nbsp;Chen Sun,&nbsp;Yong-hui Zheng,&nbsp;Wen-ying Gao,&nbsp;Lin-lin Zhao,&nbsp;Jing-yu Zhang","doi":"10.1111/cns.70153","DOIUrl":"https://doi.org/10.1111/cns.70153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate the impact of ischemic stroke (IS) on sleep homeostasis and circadian rhythms in rats, as well as the underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The middle cerebral artery occlusion model was employed to induce IS in rats. Sixty young and sixty aged rats were randomly divided into six groups for experiments. Neurological function was assessed using the Garcia score, and infarct size was evaluated through 2,3,5-triphenyltetrazolium chloride staining. Sleep–wake cycles were monitored by implanting electrodes into the neck muscles to record electroencephalograms and electromyograms. Parameters such as sleep latency, waking time, non-rapid eye movement (NREM) sleeping, rapid eye movement sleeping, NREM delta power, and waking theta power were measured. Serum cortisol and melatonin levels were measured using enzyme-linked immunosorbent assay. Gene and protein expression of circadian regulators period 1 (<i>Per1</i>) and cryptochrome 1 (<i>Cry1</i>) in the pineal gland were assessed using real-time quantitative reverse transcription polymerase chain reaction and western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the sham groups, IS-induced rats showed a decrease in Garcia scores and an increase in cerebral infarction area. Besides, relative to young rats, aged rats exhibited more severe cerebral infraction damage, lower melatonin levels, higher cortisol levels, disrupted sleep–wake cycles, and altered gene and protein expression levels of <i>Per1</i> and <i>Cry1</i> in the pineal gland.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IS can lead to neurological impairments and brain damage, with aged rats showing more severe effects. IS also disturbs melatonin and cortisol levels, affects sleep homeostasis, and results in disordered <i>Per1</i> and <i>Cry1</i> gene and protein expression levels. These findings underscore the role of circadian disruption and stress response in the pathology of IS, especially in aging populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424091","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":"Fecal Microbiota Transplantation Improves Cognitive Function of a Mouse Model of Alzheimer's Disease","authors":"Xueqin Jiang,&nbsp;Yu Zheng,&nbsp;Huaiqing Sun,&nbsp;Yini Dang,&nbsp;Mengmei Yin,&nbsp;Ming Xiao,&nbsp;Ting Wu","doi":"10.1111/cns.70259","DOIUrl":"https://doi.org/10.1111/cns.70259","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A growing body of evidence suggests a link between the gut microbiota and Alzheimer's disease (AD), although the underlying mechanisms remain elusive. This study aimed to investigate the impact of fecal microbiota transplantation (FMT) on cognitive function in a mouse model of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four-month-old 5 × FAD (familial Alzheimer's disease) mice underwent antibiotic treatment to deplete their native gut microbiota. Subsequently, they received FMT either weekly or every other day. After 8 weeks, cognitive function and β-amyloid (Aβ) load were assessed through behavioral testing and pathological analysis, respectively. The composition of the gut microbiota was analyzed using 16S rRNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Initial weekly FMT failed to alleviate memory deficits or reduce brain Aβ pathology in 5 × FAD mice. In contrast, FMT administered every other day effectively restored gut dysbiosis in 5 × FAD mice and decreased Aβ pathology and lipopolysaccharide levels in the colon and hippocampus. Mechanistically, FMT reduced the expression of amyloid β precursor protein, β-site APP cleaving enzyme 1, and presenilin-1, potentially by inhibiting the Toll-like receptor 4/inhibitor of kappa B kinase β/nuclear factor kappa-B signaling pathway. However, the cognitive benefits of FMT on 5 × FAD mice diminished over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings demonstrate the dose- and time-dependent efficacy of FMT in mitigating AD-like pathology, underscoring the potential of targeting the gut microbiota for AD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424107","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":"Anxiolytic Activity of Morellic Acid: Modulation of Diazepam's Anxiolytic Effects, Possibly Through GABAergic Interventions","authors":"Md. Shimul Bhuia,&nbsp;Tanzila Akter Eity,&nbsp;Raihan Chowdhury,&nbsp;Siddique Akber Ansari,&nbsp;Mehedi Hasan Bappi,&nbsp;Md. Anin Nayeem,&nbsp;Farjana Akter,&nbsp;Muhammad Torequl Islam","doi":"10.1111/cns.70276","DOIUrl":"https://doi.org/10.1111/cns.70276","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Numerous studies suggest that morellic acid (MOR), highly available in Garcinia plants, has different physiological activities, including anti-cancer, anti-oxidant, and anti-microbial activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In this investigation, we aimed to demonstrate the anxiolytic activity, along with the mechanism behind this activity of MOR, using in vivo and <i>in silico</i> studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this, we used different doses of MOR (5 and 10 mg/kg) and administered this drug intraperitoneally to <i>Swiss</i> albino mice (male and female). Diazepam (DZP), a positive allosteric modulator of the GABA_A receptor, was used as a positive control at a dose of 2 mg/kg (i.p), and vehicle was used as a control group. In this test, various test protocols are used to assess the behavioral patterns of mice, including swing, hole cross, light–dark testing, and open field testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This investigation revealed that MOR remarkably reduced the locomotor activity of mice in a dose-dependent manner and produced calming behaviors like DZP. However, the findings showed that the combination of MOR and DZP synergistically reduced the locomotion of mice compared to the single therapy. On the other hand, from the computational study, the result demonstrated that MOR exhibited the highest binding scores (−9.2 kcal/mol) towards the GABA_A receptor α3 subunit and −7.6 kcal/mol towards the GABA_A α2 receptor. Whereas, DZP showed −6.6 and −7.3 kcal/mol docking affinity and FLU exerted −6.2 and −6.3 kcal/mol docking scores towards the GABA_A receptor α2 and α3 subunits, respectively. The ligand interacted with the receptor by forming different hydrogen and hydrophobic bonds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>However, it is recommended that more precise and comprehensive preclinical investigations be required to demonstrate the exact mechanism behind the anxiolytic effects and conduct clinical trials to determine efficacy and safety.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424105","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":"Panaxadiol Attenuates Neuronal Oxidative Stress and Apoptosis in Cerebral Ischemia/Reperfusion Injury via Regulation of the JAK3/STAT3/HIF-1α Signaling Pathway","authors":"Jiabin Zhou,&nbsp;Yu Lei,&nbsp;Shilin Zhang,&nbsp;Yuhan Liu,&nbsp;Dongye Yi","doi":"10.1111/cns.70233","DOIUrl":"https://doi.org/10.1111/cns.70233","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cerebral ischemic stroke (CIS) is a debilitating neurological condition lacking specific treatments. Cerebral ischemia/reperfusion injury (CIRI) is a critical pathological process in CIS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This study aimed to explore the protective effects of panaxadiol (PD) against oxidative stress-induced neuronal apoptosis in CIS/CIRI and its underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>An MCAO mouse model was established to investigate the therapeutic effects of PD in vivo. Network pharmacology and molecular docking techniques were used to predict PD's anti-CIS targets. The protective effects of PD were further validated in vitro using oxygen–glucose deprivation/reoxygenation (OGD/R)-treated HT22 cells. Finally, core targets were verified through combined in vivo and in vitro experiments to elucidate the mechanisms of PD in treating CIS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>PD exhibited significant neuroprotective activity, demonstrated by restoration of behavioral performance, reduced infarct volume, and decreased neuronal apoptosis in mice. Network pharmacology analysis identified 24 overlapping target genes between PD and CIS-related targets. The hub genes, PTGS2, SERPINE1, ICAM-1, STAT3, MMP3, HMOX1, and NOS3, were associated with the HIF-1α pathway, which may play a crucial role in PD's anti-CIS effects. Molecular docking confirmed the stable binding of PD to these hub genes. Both in vitro and in vivo experiments further confirmed that PD significantly mitigates neuronal apoptosis and oxidative stress induced by CIS/CIRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PD significantly counteracts CIS/CIRI by modulating the JAK3/STAT3/HIF-1α signaling pathway, making it a promising therapeutic agent for treating CIS/CIRI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424106","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}