CNS Neuroscience & Therapeutics最新文献

{"title":"Microglial Melatonin Receptor 1 Degrades Pathological Alpha-Synuclein Through Activating LC3-Associated Phagocytosis In Vitro","authors":"Xiao-Yu Yao,&nbsp;Bing-Er Cao,&nbsp;Jun-Yi Liu,&nbsp;Qian-Kun Lv,&nbsp;Jia-Rui Zhang,&nbsp;Xiao-Yu Cheng,&nbsp;Cheng-Jie Mao,&nbsp;Quan-Hong Ma,&nbsp;Fen Wang,&nbsp;Chun-Feng Liu","doi":"10.1111/cns.70088","DOIUrl":"10.1111/cns.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs), primarily constituted of α-synuclein (α-Syn). Microglial cells exhibit specific reactivity toward misfolded proteins such as α-Syn. However, the exact clearance mechanism and related molecular targets remain elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>BV2 cells, primary microglia from wild-type and MT1 knockout mice, and primary cortical neurons were utilized as experimental models. The study investigated relevant mechanisms by modulating microglial MT1 expression through small RNA interference (RNAi) and lentiviral overexpression techniques. Furthermore, pathological aggregation of α-Syn was induced using pre-formed fibrils (PFF) α-Syn. Co-immunoprecipitation, immunofluorescence, Western blot (WB), and quantitative real-time PCR were used to elucidate the mechanisms of molecular regulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, we elucidated the regulatory role of the melatonin receptor 1 (MT1) in the microglial phagocytic process. Following MT1 knockout, the ability of microglial cells to engulf latex beads and zymosan particles decreased, subsequently affecting the phagocytic degradation of fibrillar α-Syn by microglial cells. Furthermore, the loss of MT1 receptors in microglial cells exacerbates the aggregation of α-Syn in neurons induced by pre-formed fibrils (PFF) α-Syn. Mechanistically, MT1 influences the phagocytic function of microglial cells by regulating the Rubicon-dependent LC3-associated phagocytosis (LAP) pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, the results suggest the neuroprotective function of microglial cells in clearing α-Syn through MT1-mediated LAP, highlighting the potential key role of MT1 in pathogenic mechanisms associated with α-Syn.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491616","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":"Spinal Adhesive Arachnoidopathy, the Disorder More Than Simply Adhesive Arachnoiditis: A Comprehensive Systematic Review of 510 Cases","authors":"Weikang Zhang,&nbsp;Zhenlei Liu,&nbsp;Kai Wang,&nbsp;Lei Zhang,&nbsp;Shaocheng Liu,&nbsp;Xiangyu Zhang,&nbsp;Yutian Wang,&nbsp;Kun He,&nbsp;Hao Wu","doi":"10.1111/cns.70084","DOIUrl":"10.1111/cns.70084","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;Spinal adhesive arachnoidopathy (SAA) is a chronic pathology associated with persistent inflammatory responses in the arachnoid. Adhesive arachnoiditis (AA) is one of the major forms of SAA, with accompanying secondary complications. Therefore, we aimed to systematically review both clinical and animal model studies related to SAA to gain a deeper understanding of this unique pathology.&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;A literature search was conducted in PubMed, EMBASE, and Cochrane Library databases to retrieve relevant publications up to October 2022. Clinical manifestations, etiologies, imaging modalities, treatments, and prognosis in patients with SAA were collected. Data from animal experiments related to SAA were also extracted.&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;A total of 176 studies, including 147 clinical and 29 animal model studies, with a total of 510 patients were enrolled in this study. Pain (37.5%), abnormal nerve sensations (39.58%), and abnormal motor function (78.75%) were the top three common symptoms of SAA. Major etiologies included trauma (22.7%), infection (17.73%), surgery (15.37%), and hemorrhage (13.48%). MRI was widely used to confirm the diagnosis. AA could be involved in cervical (96/606, 15.84%), thoracic (297/606, 49.01%), lumbar (174/606, 28.71%), and sacrococcygeal (39/606, 6.44%) vertebral segments. Patients with AA in cervical segments had a higher post-surgery recovery rate (&lt;i&gt;p&lt;/i&gt; = 0.016) compared to that of other segments. The common pathological diagnoses of SAA were AA (80.82%), AA combined with arachnoid cyst (12.79%), arachnoid calcification/scars (3.43%), and arachnoid web/fibrosis (2.97%). Patients with AA were more likely to develop syringomyelia, compared with patients with other forms of SAA (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Animal studies mainly focused on new AA therapeutic agents (&lt;i&gt;n&lt;/i&gt; = 14), the pathomechanism of AA (&lt;i&gt;n&lt;/i&gt; = 14), and the development of new MRI sequences for improved diagnosis (&lt;i&gt;n&lt;/i&gt; = 1).&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;The pathological consequences of SAA are more complex than AA and manifest in different forms, such as AA combined with arachnoid cyst, arachnoid calcification/scars, and arachnoid web/fibrosis. In many instances, AA was associated with secondary syringomyelia. Unspecific clinical manifestations of SAA may easily lead to misdiagnosis and missed diagnosis. Although SAA may result from multiple etiologies, including spinal trauma, meningitis, spinal surgery, and hemorrhage, the pathog","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454188","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":"Inhibiting endoplasmic reticulum stress alleviates perioperative neurocognitive disorders by reducing neuroinflammation mediated by NLRP3 inflammasome activation","authors":"Fanbing Meng,&nbsp;Jian Song,&nbsp;Xinwei Huang,&nbsp;Meixian Zhang,&nbsp;Xiaoxiao Sun,&nbsp;Qi Jing,&nbsp;Silu Cao,&nbsp;Zheng Xie,&nbsp;Qiong Liu,&nbsp;Hui Zhang,&nbsp;Cheng Li","doi":"10.1111/cns.70049","DOIUrl":"10.1111/cns.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study is to explore the key mechanisms of perioperative neurocognitive dysfunction (PND) after anesthesia/surgery (A/S) by screening hub genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Transcriptome sequencing was conducted on hippocampal samples obtained from 18-month-old C57BL/6 mice assigned to control (Ctrl) and A/S groups. The functionality of differentially expressed genes (DEGs) was investigated using Metascape. Hub genes associated with changes between the two groups were screened by combining weighted gene coexpression network analysis within CytoHubba. Reverse transcription PCR and western blotting were used to validate changes in mRNA and protein expression, respectively. NLRP3 inflammasome activation was detected by western blotting and ELISA. Tauroursodeoxycholic acid (TUDCA), an inhibitor of endoplasmic reticulum (ER) stress, was administrated preoperatively to explore its effects on the occurrence of PND. Immunofluorescence analysis was performed to evaluate the activation of astrocytes and microglia in the hippocampus, and hippocampus-dependent learning and memory were assessed using behavioral experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 521 DEGs were detected between the control and A/S groups. These DEGs were significantly enriched in biological processes related to metabolic processes and their regulation. Four hub genes (<i>Hspa5</i>, <i>Igf1r</i>, <i>Sfpq</i>, and <i>Xbp1</i>) were identified. Animal experiments have shown that mice in the A/S group exhibited cognitive impairments accompanied by increased <i>Hspa5</i> and <i>Xbp1</i> expression, ER stress, and activation of NLRP3 inflammasome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Inhibiting ER stress alleviated cognitive impairment in A/S mice; particularly, ER stress induced by A/S results in NLRP3 inflammasome activation and neuroinflammation. Moreover, the preoperative administration of TUDCA inhibited ER stress, NLRP3 inflammasome activation, and neuroinflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454186","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":"Cerebral small vessel disease was associated with the prognosis in ischemic stroke with atrial fibrillation","authors":"Yicong Wang,&nbsp;Hang Li,&nbsp;Yuesong Pan,&nbsp;Mengxing Wang,&nbsp;Xiaoling Liao,&nbsp;Yingying Yang,&nbsp;Weiqi Chen,&nbsp;Xia Meng,&nbsp;Yongjun Wang,&nbsp;Yilong Wang","doi":"10.1111/cns.70052","DOIUrl":"10.1111/cns.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The purpose of this study was to explore the relationship between atrial fibrillation (AF), cerebral small vessel disease (CSVD), and ischemic stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were extracted from China's Third National Stroke Registry (CNSR-III), which registered 15,166 patients in China. A total of 12,180 ischemic stroke patients were included excluding those diagnosed with TIA or without MRI. Logistic regression was to explore the relationship between AF, CSVD, and poor functional outcomes at 12-month follow-up. Cox regression is to explore AF, CSVD, and stroke recurrence as well as all-cause mortality at 12-month follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The average age was 62.40 ± 11.22 years old, and 8362 (68.65%) were men at baseline. Patients with AF had an increased risk of stroke recurrence and all-cause mortality at 12-month follow-up. Those with AF and CSVD imaging such as lacunes, white matter hyperintensity (WMH), and the presence of cerebral microbleeds (CMBs) had an increased risk of poor prognosis. And those with both AF and CSVD burden had an increased risk of worse prognosis at 12-month follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Among Chinese patients with acute ischemic stroke, those with AF were associated with a higher risk of 12-month mortality and stroke recurrence. When AF was combined with some CSVD imaging features such as lacunes, WMH, presence of CMBs or burdens, the 12-month poor prognosis worsened.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454184","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":"Exploratory Analysis of the Association Between Plasma Ceramide Alterations and Cognitive Dysfunction in Parkinson's Disease","authors":"Xu Liu,&nbsp;Xuanjing Liu,&nbsp;Yuning Liu,&nbsp;Bo Yang,&nbsp;Yangdanyu Li,&nbsp;Fujia Li,&nbsp;Kun Qian,&nbsp;Xuesong Liu,&nbsp;Lishun Xiao,&nbsp;Guiyun Cui,&nbsp;Chuanying Xu","doi":"10.1111/cns.70082","DOIUrl":"10.1111/cns.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Prior research has underscored the importance of sphingolipid metabolism in Parkinson's disease (PD) pathogenesis. Our objective was to explore the associations between plasma ceramide levels and PD patients with cognitive dysfunction (PD-CD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled two study populations from Eastern China and the Parkinson's Progression Markers Initiative (PPMI), comprising 290 (100 HCs, 160 PDs, and 30 MSAs) and 429 (125 HCs and 304 PDs) participants, respectively. The plasma levels of ceramides (Cer 16:0, Cer 18:0, Cer 24:0, and Cer 24:1) were tested via HPLC–MS/MS analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with those in the HC group, the plasma levels of Cer 18:0, Cer 24:1, Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0 were higher in both the PD and MSA groups. Significant differences in the plasma levels of Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0 were observed among the PD-NC (PD with normal cognition), PD-MCI (PD with mild cognitive impairment), and PDD (PD dementia) groups, with the PDD group exhibiting the highest levels. PD patients with higher baseline levels of plasma ceramides (specifically, Cer 18:0, Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0) demonstrated accelerated cognitive decline compared with individuals who had lower baseline plasma ceramide levels during the 5-year follow-up period. A biomarker panel including Cer 18:0/Cer 24:0 and Cer 24:1/Cer 24:0 could effectively differentiate PD-CD from PD-NC with notable diagnostic accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicate that plasma ceramide levels could potentially be used as diagnostic biomarkers for PD-CD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454185","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":"Novel Insights Into DLAT's Role in Alzheimer's Disease-Related Copper Toxicity Through Microglial Exosome Dynamics","authors":"Xiang Ma,&nbsp;Yusheng Sun,&nbsp;Changchun Li,&nbsp;Man Wang,&nbsp;Qijiao Zang,&nbsp;Xuxia Zhang,&nbsp;Feng Wang,&nbsp;Yulan Niu,&nbsp;Jiai Hua","doi":"10.1111/cns.70064","DOIUrl":"10.1111/cns.70064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a complex neurodegenerative disorder, with recent research emphasizing the roles of microglia and their secreted extracellular vesicles in AD pathology. However, the involvement of specific molecular pathways contributing to neuronal death in the context of copper toxicity remains largely unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigates the interaction between pyruvate kinase M2 (PKM2) and dihydrolipoamide S-acetyltransferase (DLAT), particularly focusing on copper-induced neuronal death in Alzheimer's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Gene expression datasets were analyzed to identify key factors involved in AD-related copper toxicity. The role of DLAT was validated using 5xFAD transgenic mice, while in vitro experiments were conducted to assess the impact of microglial exosomes on neuronal PKM2 transfer and DLAT expression. The effects of inhibiting the PKM2 transfer via microglial exosomes on DLAT expression and copper-induced neuronal death were also evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DLAT was identified as a critical factor in the pathology of AD, particularly in copper toxicity. In 5xFAD mice, increased DLAT expression was linked to hippocampal damage and cognitive decline. In vitro, microglial exosomes were shown to facilitate the transfer of PKM2 to neurons, leading to upregulation of DLAT expression and increased copper-induced neuronal death. Inhibition of PKM2 transfer via exosomes resulted in a significant reduction in DLAT expression, mitigating neuronal death and slowing AD progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study uncovers a novel pathway involving microglial exosomes and the PKM2-DLAT interaction in copper-induced neuronal death, providing potential therapeutic targets for Alzheimer's disease. Blocking PKM2 transfer could offer new strategies for reducing neuronal damage and slowing disease progression in AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454187","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":"Therapeutic approaches targeting aging and cellular senescence in Huntington's disease","authors":"Asif Ahmad Bhat,&nbsp;Ehssan Moglad,&nbsp;Muhammad Afzal,&nbsp;Riya Thapa,&nbsp;Waleed Hassan Almalki,&nbsp;Imran Kazmi,&nbsp;Sami I. Alzarea,&nbsp;Haider Ali,&nbsp;Kumud Pant,&nbsp;Thakur Gurjeet Singh,&nbsp;Harish Dureja,&nbsp;Sachin Kumar Singh,&nbsp;Kamal Dua,&nbsp;Gaurav Gupta,&nbsp;Vetriselvan Subramaniyan","doi":"10.1111/cns.70053","DOIUrl":"10.1111/cns.70053","url":null,"abstract":"<p>Huntington's disease (HD) is a devastating neurodegenerative disease that is manifested by a gradual loss of physical, cognitive, and mental abilities. As the disease advances, age has a major impact on the pathogenic signature of mutant huntingtin (mHTT) protein aggregation. This review aims to explore the intricate relationship between aging, mHTT toxicity, and cellular senescence in HD. Scientific data on the interplay between aging, mHTT, and cellular senescence in HD were collected from several academic databases, including PubMed, Google Scholar, Google, and ScienceDirect. The search terms employed were “AGING,” “HUNTINGTON'S DISEASE,” “MUTANT HUNTINGTIN,” and “CELLULAR SENESCENCE.” Additionally, to gather information on the molecular mechanisms and potential therapeutic targets, the search was extended to include relevant terms such as “DNA DAMAGE,” “OXIDATIVE STRESS,” and “AUTOPHAGY.” According to research, aging leads to worsening HD pathophysiology through some processes. As a result of the mHTT accumulation, cellular senescence is promoted, which causes DNA damage, oxidative stress, decreased autophagy, and increased inflammatory responses. Pro-inflammatory cytokines and other substances are released by senescent cells, which may worsen the neuronal damage and the course of the disease. It has been shown that treatments directed at these pathways reduce some of the HD symptoms and enhance longevity in experimental animals, pointing to a new possibility of treating the condition. Through their amplification of the harmful effects of mHTT, aging and cellular senescence play crucial roles in the development of HD. Comprehending these interplays creates novel opportunities for therapeutic measures targeted at alleviating cellular aging and enhancing HD patients’ quality of life.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454189","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":"Insulin-Like Growth Factor Binding Protein 2 Drives Neurodegeneration in Parkinson's Disease: Insights From In Vivo and In Vitro Studies","authors":"Jing An,&nbsp;Lulu Wen,&nbsp;Haiyang Yu,&nbsp;Zhongqi Bu,&nbsp;Juan Feng","doi":"10.1111/cns.70076","DOIUrl":"https://doi.org/10.1111/cns.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Insulin-like growth factor binding protein 2 (IGFBP2) is implicated in various neurodegenerative diseases. However, its role in Parkinson's disease (PD) is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PD rat model was established by 6-OHDA injection. After 3 weeks, mRNA-seq was conducted. Rats received rIGFBP2 via intra-MFB injection 6 h prior to 6-OHDA infusion, and the effect of IGFBP2 in PD rats was investigated by western blotting, IHC, specific kits, JC-1 staining, and TUNEL analysis. In vitro, PC12 cells were treated with 6-OHDA, and CCK-8, specific kits, Hoechst 33258 staining, Western blotting, and JC-1 staining were performed to assess the IGFBP2's role.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>mRNA-seq revealed DEGs in PD, with attention to downregulated IGFBP2. rIGFBP2 treatment aggravated neurobehavioral deficits, decreased TH expression, Ψm, ATP level and SOD, GSH-Px activities but increased α-synuclein, ROS, MDA, mitochondrial cytochrome <i>c</i> contents, cell apoptosis in 6-OHDA-lesioned rats, which might be mediated through inactivating IGF-1R/AKT pathway. In 6-OHDA-treated PC12 cells, rIGFBP2 aggravated cell injury, demonstrated by decreased cell viability and increased apoptosis, oxidative stress, and mitochondrial dysfunction. Co-treatment with rIGFBP2 and rIGF-1 partially reversed the effect of rIGFBP2 on cell damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IGFBP2 exacerbates neurodegeneration in PD through increasing oxidative stress, mitochondrial dysfunction, and apoptosis via inhibiting IGF-1R/AKT pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443392","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":"Olfactory bulb stimulation mitigates Alzheimer's-like disease progression","authors":"Morteza Salimi,&nbsp;Milad Nazari,&nbsp;Payam Shahsavar,&nbsp;Samaneh Dehghan,&nbsp;Mohammad Javan,&nbsp;Javad Mirnajafi-Zadeh,&nbsp;Mohammad Reza Raoufy","doi":"10.1111/cns.70056","DOIUrl":"https://doi.org/10.1111/cns.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Deep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimer's disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Our study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (Aβ) AD model rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimer's-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by the evaluations of histological, behavioral, and local field potential signal processing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>OB stimulation counteracted Aβ plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435489","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":"Identifying modifiable factors associated with neuroimaging markers of brain health","authors":"Liang-Yu Huang,&nbsp;Yan Fu,&nbsp;Yi Zhang,&nbsp;He-Ying Hu,&nbsp;Ling-Zhi Ma,&nbsp;Yi-Jun Ge,&nbsp;Yong-Li Zhao,&nbsp;Ya-Ru Zhang,&nbsp;Shi-Dong Chen,&nbsp;Jian-Feng Feng,&nbsp;Wei Cheng,&nbsp;Lan Tan,&nbsp;Jin-Tai Yu","doi":"10.1111/cns.70057","DOIUrl":"https://doi.org/10.1111/cns.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Brain structural alterations begin long before the presentation of brain disorders; therefore, we aimed to systematically investigate a wide range of influencing factors on neuroimaging markers of brain health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing data from 30,651 participants from the UK Biobank, we explored associations between 218 modifiable factors and neuroimaging markers of brain health. We conducted an exposome-wide association study using the least absolute shrinkage and selection operator (LASSO) technique. Restricted cubic splines (RCS) were further employed to estimate potential nonlinear correlations. Weighted standardized scores for neuroimaging markers were computed based on the estimates for individual factors. Finally, stratum-specific analyses were performed to examine differences in factors affecting brain health at different ages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The identified factors related to neuroimaging markers of brain health fell into six domains, including systematic diseases, lifestyle factors, personality traits, social support, anthropometric indicators, and biochemical markers. The explained variance percentage of neuroimaging markers by weighted standardized scores ranged from 0.5% to 7%. Notably, associations between systematic diseases and neuroimaging markers were stronger in older individuals than in younger ones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identified a series of factors related to neuroimaging markers of brain health. Targeting the identified factors might help in formulating effective strategies for maintaining brain health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435490","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}