ACS Chemical Neuroscience最新文献_第6页

Exogenous Amyloid Fibrils Can Cause Significant Upregulation of Neurodegenerative Disease Proteins. 外源性淀粉样蛋白纤维可导致神经退行性疾病蛋白的显著上调。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 Epub Date: 2024-10-18 DOI: 10.1021/acschemneuro.4c00483

Xihua Liu, Wenzhe Jia, Yapeng Fang, Yiping Cao

{"title":"Exogenous Amyloid Fibrils Can Cause Significant Upregulation of Neurodegenerative Disease Proteins.","authors":"Xihua Liu, Wenzhe Jia, Yapeng Fang, Yiping Cao","doi":"10.1021/acschemneuro.4c00483","DOIUrl":"10.1021/acschemneuro.4c00483","url":null,"abstract":"Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are associated with the formation of amyloid fibrils. In familial cases, the mutant causative genes accentuate disease progression through overexpression or misfolding of amyloidogenic proteins. Besides, considerable amyloidosis cases arise from external factors, but their origin and mechanisms are not yet fully understood. Herein, we found that amyloid fibrils generated from egg and milk proteins, in addition to their nutritional effects to intestinal cells, can selectively reduce the viability of nervous cells as well as pancreatic islet cells. In contrast, soy protein amyloid fibrils lacked cytotoxicity to the aforementioned cells. This protein source and cell type-dependent cytotoxicity are demonstrated to be associated with the significant upregulation of amyloidogenic proteins. The finding was also confirmed by the vein injection of beta-lactoglobulin fibrils to mice, exhibiting the pronounced upregulations of amyloid beta1-42 (Aβ1-42) and islet amyloid polypeptide in vivo. The study therefore provides insight into the health implications of exogenous amyloid fibrils.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"4284-4294"},"PeriodicalIF":4.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cross-Interactions of Aβ Peptides Implicated in Alzheimer's Disease Shape Amyloid Oligomer Structures and Aggregation. 与阿尔茨海默病有关的 Aβ 肽的交叉相互作用会形成淀粉样蛋白寡聚体结构和聚集。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 Epub Date: 2024-11-19 DOI: 10.1021/acschemneuro.4c00492

Tanja Habeck, Silvana Smilla Zurmühl, António J Figueira, Edvaldo Vasconcelos Soares Maciel, Cláudio M Gomes, Frederik Lermyte

{"title":"Cross-Interactions of Aβ Peptides Implicated in Alzheimer's Disease Shape Amyloid Oligomer Structures and Aggregation.","authors":"Tanja Habeck, Silvana Smilla Zurmühl, António J Figueira, Edvaldo Vasconcelos Soares Maciel, Cláudio M Gomes, Frederik Lermyte","doi":"10.1021/acschemneuro.4c00492","DOIUrl":"10.1021/acschemneuro.4c00492","url":null,"abstract":"A defining hallmark of Alzheimer's disease (AD) is the synaptic aggregation of the amyloid β (Aβ) peptide. In vivo, Aβ production results in a diverse mixture of variants, of which Aβ40, Aβ42, and Aβ43 are profusely present in the AD brain, and their relative abundance is recognized to play a role in disease onset and progression. Nonetheless, the occurrence of Aβ40, Aβ42, and Aβ43 hetero-oligomerization and the subsequent effects on Aβ aggregation remain elusive and were investigated here. Using thioflavin-T (ThT)-monitored aggregation assays and native mass spectrometry coupled to ion mobility analysis (IM-MS), we first show that all Aβ peptides are aggregation-competent and self-assemble into homo-oligomers with distinct conformational populations, which are more pronounced between Aβ40 than the longer variants. ThT assays were then conducted on binary mixtures of Aβ variants, revealing that Aβ42 and Aβ43 aggregate independently from Aβ40 but significantly speed up Aβ40 fibrillation. Aβ42 and Aβ43 were observed to aggregate concurrently and mutually accelerate fibril formation, which likely involves hetero-oligomerization. Accordingly, native MS analysis revealed pairwise oligomerization between all variants, with the formation of heterodimers and heterotrimers. Interestingly, IM-MS indicates that hetero-oligomers containing longer Aβ variants are enriched in conformers with lower collision cross-sections when compared to their homo-oligomer counterparts. This suggests that Aβ42 and Aβ43 are capable of remodeling the oligomer structure toward a higher compaction level. Altogether, our findings provide a mechanistic description for the hetero-oligomerization of Aβ variants implicated in AD, contributing to rationalizing their in vivo proteotoxic interplay.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"4295-4304"},"PeriodicalIF":4.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring Cimetidine as a Potential Therapeutic Attenuator against Amyloid Formation in Parkinson’s Disease: Spectroscopic and Microscopic Insights into Alpha-Synuclein and Human Insulin

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 DOI: 10.1021/acschemneuro.4c0058810.1021/acschemneuro.4c00588

Md Nadir Hassan, Azeem Ahmad, Murtaza Hussain, Suhani Gupta, Huzaifa Yasir Khan, Tariq Aziz and Rizwan Hasan Khan*,

{"title":"Exploring Cimetidine as a Potential Therapeutic Attenuator against Amyloid Formation in Parkinson’s Disease: Spectroscopic and Microscopic Insights into Alpha-Synuclein and Human Insulin","authors":"Md Nadir Hassan, Azeem Ahmad, Murtaza Hussain, Suhani Gupta, Huzaifa Yasir Khan, Tariq Aziz and Rizwan Hasan Khan*, ","doi":"10.1021/acschemneuro.4c0058810.1021/acschemneuro.4c00588","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00588https://doi.org/10.1021/acschemneuro.4c00588","url":null,"abstract":"Neurodegenerative diseases, notably Alzheimer’s and Parkinson’s, hallmark their progression through the formation of amyloid aggregates resulting from misfolding. While current therapeutics alleviate symptoms, they do not impede disease onset. In this context, repurposing existing drugs stands as a viable therapeutic strategy. Our study determines the antihistamine drug Cimetidine’s potential as an inhibitor using diverse spectroscopic and microscopic methods on alpha-synuclein and human insulin amyloid formation, unveiling its efficacy. The thioflavin T (ThT) assay illustrated a dose-dependent reduction in amyloid formation with escalating concentrations of Cimetidine. Notably, the antihistamine drug maintained a helical structure and showed no significant conformational changes in the secondary structure. Confocal microscopy validated fewer fibrils in the Cimetidine-treated samples. Remarkably, Cimetidine interacted with pre-existing fibrils, leading to their disintegration. Further analyses (ThT, circular dichroism, and dynamic light scattering) showcased the conversion of fibrils into smaller aggregates upon Cimetidine addition. These findings signify the potential of this antihistamine drug as a plausible therapeutic option for Parkinson’s disease. This study may open avenues for deeper investigations and possible therapeutic developments, emphasizing Cimetidine’s promising role in mitigating neurodegenerative diseases like Parkinson’s.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4517–4532 4517–4532"},"PeriodicalIF":4.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

1H NMR-Based Metabolomic Signatures in Rodent Models of Sporadic Alzheimer’s Disease and Metabolic Disorders

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 DOI: 10.1021/acschemneuro.4c0051010.1021/acschemneuro.4c00510

Ananya Shukla, Khushbhu Meena, Ashish Gupta and Rajat Sandhir*,

{"title":"1H NMR-Based Metabolomic Signatures in Rodent Models of Sporadic Alzheimer’s Disease and Metabolic Disorders","authors":"Ananya Shukla, Khushbhu Meena, Ashish Gupta and Rajat Sandhir*, ","doi":"10.1021/acschemneuro.4c0051010.1021/acschemneuro.4c00510","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00510https://doi.org/10.1021/acschemneuro.4c00510","url":null,"abstract":"Alzheimer’s disease (AD) is a chronic neurological disorder that impacts the elderly population all over the globe. Evidence suggests association between AD and metabolic disorders such as diabetes mellitus (DM) and obesity (OB). The present study is an attempt to evaluate metabolic alterations in the serum and brain through NMR spectroscopy with the aim to identify shared metabolic signatures. AD was induced in rats by stereotactic intracerebroventricular injection of oligomerized Aβ-42 peptide into the brain. DM and OB were induced by intraperitoneal injection of streptozotocin and feeding rats on a high-fat diet, respectively. The metabolic alterations obtained through 1H NMR spectroscopy were further subjected to multivariate analysis by principal component analysis and partial least-squares discrimination for identification of metabolic signatures. In the serum, the levels of lactate and betaine were increased in AD, DM, and OB rats. On the other hand, the metabolite profile of brain indicated increase in the levels of lactate, N-acetylaspartate, and creatinine in AD, DM, and OB rats. Additionally, the concentration of neurochemicals such as glutamate, GABA, N-acetylglutamate, and myo-inositol were also elevated. The alterations in neurotransmitters and cerebral energy metabolism were accompanied by deficits in cognition assessed by Morris water maze in AD, DM, and OB rats. The perturbed metabolic profiles were accompanied by the presence of pathogenic amyloid deposits visualized by Congo red stain in the brains of AD, DM, and OB rats. Overall, the study identifies common metabolic signatures in AD, DM, and OB that may be involved in etiopathogenesis and also suggests linkages between these three conditions.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4478–4499 4478–4499"},"PeriodicalIF":4.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to “Design, Synthesis, and Activity of an α-Conotoxin LtIA Fluorescent Analogue”

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 DOI: 10.1021/acschemneuro.4c0077610.1021/acschemneuro.4c00776

Yishuai Yang, Yao Tan, Dongting Zhangsun, Xiaopeng Zhu* and Sulan Luo*,

引用次数: 0

Rimota-Gd: Paramagnetic Probe for In Vivo MRI Studies of the Cannabinoid 1 Receptor Distribution in the Mouse Brain. Rimota-Gd：顺磁探针用于小鼠脑内大麻素 1 受体分布的体内磁共振成像研究。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 Epub Date: 2024-11-14 DOI: 10.1021/acschemneuro.4c00259

Qi Ouyang, Fei Zhao, Jingjing Ye, Mengyang Xu, Suyun Pu, Wenxue Hui, Xinyan Gao, Xiaochuan Zha, Hao Chen, Zhiming Wang, Fei Li, Zonghua Luo, Kurt Wüthrich, Garth J Thompson

{"title":"Rimota-Gd: Paramagnetic Probe for In Vivo MRI Studies of the Cannabinoid 1 Receptor Distribution in the Mouse Brain.","authors":"Qi Ouyang, Fei Zhao, Jingjing Ye, Mengyang Xu, Suyun Pu, Wenxue Hui, Xinyan Gao, Xiaochuan Zha, Hao Chen, Zhiming Wang, Fei Li, Zonghua Luo, Kurt Wüthrich, Garth J Thompson","doi":"10.1021/acschemneuro.4c00259","DOIUrl":"10.1021/acschemneuro.4c00259","url":null,"abstract":"The cannabinoid 1 receptor (CB1) is highly expressed in the central nervous system, where its physiological functions include the regulation of energy balance, pain, and addiction. Herein, we develop and validate a technique to use magnetic resonance imaging (MRI) to investigate the distribution of CB1 across mouse brains with high spatial resolution, expanding previously described in vitro studies and in vivo studies with positron emission tomography (PET). To support the MRI investigations, we developed a ligand that is specific for in vivo neuroimaging of CB1. By chemically conjugating the CB1 antagonist rimonabant acid to a gadolinium chelator, we obtained the paramagnetic probe Rimota-Gd. The specificity of binding of rimonabant acid to CB1 and the relaxation enhancement by the paramagnetic gadolinium permit MRI-based localization of CB1. We used Rimota-Gd to investigate the spatial distribution of CB1 across the mouse brain and compared the results with an investigation using the PET radioligand [18F]MK-9470. Rimota-Gd opens the door for in vivo MRI imaging of CB1 and provides a roadmap for the study of other receptors by whole-brain images with high spatial and temporal resolution.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"4258-4266"},"PeriodicalIF":4.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathological Mutations D169G and P112H Electrostatically Aggravate the Amyloidogenicity of the Functional Domain of TDP-43. 病理突变 D169G 和 P112H 会静电加剧 TDP-43 功能域的淀粉样形成。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 Epub Date: 2024-11-18 DOI: 10.1021/acschemneuro.4c00372

Meenakshi Pillai, Anjali D Patil, Atanu Das, Santosh Kumar Jha

{"title":"Pathological Mutations D169G and P112H Electrostatically Aggravate the Amyloidogenicity of the Functional Domain of TDP-43.","authors":"Meenakshi Pillai, Anjali D Patil, Atanu Das, Santosh Kumar Jha","doi":"10.1021/acschemneuro.4c00372","DOIUrl":"10.1021/acschemneuro.4c00372","url":null,"abstract":"Aggregation of TDP-43 is linked to the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, electrostatic point mutations such as D169G and P112H, located within the highly conserved functional tandem RNA recognition motif (RRM) domains of the TDP-43 protein (TDP-43tRRM), have been identified in diseased patients as well. In this study, we address how the electrostatic mutations alter both the native state stability and aggregation propensity of TDP-43tRRM. The mutants D169G and P112H show increased chemical stability compared to the TDP-43tRRM at physiological pH. However, at low pH, both the mutants undergo a conformational change to form amyloid-like fibrils, though with variable rates─the P112H mutant being substantially faster than the other two sequences (TDP-43tRRM and D169G mutant) showing comparable rates. Moreover, among the three sequences, only the P112H mutant undergoes a strong ionic strength-dependent aggregability trend. These observations signify the substantial contribution of the excess charge of the P112H mutant to its unique aggregation process. Complementary simulated observables with atomistic resolution assign the experimentally observed sequence-, pH-, and ionic strength-dependent aggregability pattern to the degree of thermal lability of the mutation site-containing RRM1 domain and its extent of dynamical anticorrelation with the RRM2 domain whose combination eventually dictate the extent of generation of aggregation-prone partially unfolded conformational ensembles. Our choice of a specific charge-modulated pathogenic mutation-based experiment-simulation-combination approach unravels the otherwise hidden residue-wise contribution to the individual steps of this extremely complicated multistep aggregation process.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"4267-4283"},"PeriodicalIF":4.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the Monomeric and Dimeric Conformational Landscapes of the Full-Length TDP-43 and the Impact of the C-Terminal Domain. 解密全长 TDP-43 的单体和二聚体构象景观以及 C 端结构域的影响

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 Epub Date: 2024-11-16 DOI: 10.1021/acschemneuro.4c00557

Vaishnavi Tammara, Abhilasha A Doke, Santosh Kumar Jha, Atanu Das

{"title":"Deciphering the Monomeric and Dimeric Conformational Landscapes of the Full-Length TDP-43 and the Impact of the C-Terminal Domain.","authors":"Vaishnavi Tammara, Abhilasha A Doke, Santosh Kumar Jha, Atanu Das","doi":"10.1021/acschemneuro.4c00557","DOIUrl":"10.1021/acschemneuro.4c00557","url":null,"abstract":"The aberrant aggregation of TAR DNA-binding protein 43 kDa (TDP-43) in cells leads to the pathogenesis of multiple fatal neurodegenerative diseases. Decoding the proposed initial transition between its functional dimeric and aggregation-prone monomeric states can potentially design a viable therapeutic strategy, which is presently limited by the lack of structural detail of the full-length TDP-43. To achieve a complete understanding of such a delicate phase space, we employed a multiscale simulation approach that unearths numerous crucial features, broadly summarized in two categories: (1) state-independent features that involve inherent chain collapsibility, rugged polymorphic landscape dictated by the terminal domains, high β-sheet propensity, structural integrity preserved by backbone-based intrachain hydrogen bonds and electrostatic forces, the prominence of the C-terminal domain in the intrachain cross-domain interfaces, and equal participation of hydrophobic and hydrophilic (charged and polar) residues in cross-domain interfaces; and (2) dimerization-modulated characteristics that encompass slower collapsing dynamics, restricted polymorphic landscape, the dominance of side chains in interchain hydrogen bonds, the appearance of the N-terminal domain in the dimer interface, and the prominence of hydrophilic (specifically polar) residues in interchain homo- and cross-domain interfaces. In our work, the ill-known C-terminal domain appears as the most crucial structure-dictating domain, which preferably populates a compact conformation with a high β-sheet propensity in its isolated state stabilized by intrabackbone hydrogen bonds, and these signatures are comparatively faded in its integrated form. Validation of our simulated observables by a complementary spectroscopic approach on multiple counts ensures the robustness of the computationally predicted features of the TDP-43 aggregation landscape.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"4305-4321"},"PeriodicalIF":4.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging Frontiers in Conformational Exploration of Disordered Proteins: Integrating Autoencoder and Molecular Simulations. 无序蛋白质构象探索的新前沿：自动编码器与分子模拟的整合。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-12-04 Epub Date: 2024-11-18 DOI: 10.1021/acschemneuro.4c00670

Jiyuan Zeng, Zhongyuan Yang, Yiming Tang, Guanghong Wei

引用次数: 0

Visualization of Unconjugated Bilirubin In Vivo with a Novel Approach Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging in a Rat Model

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-30 DOI: 10.1021/acschemneuro.4c0060410.1021/acschemneuro.4c00604

Lin Yang, Yan Cheng, Yanlong Jia, Zhen Cao, Zerui Zhuang, Xiaolei Zhang, Jitian Guan, Rongzhi Cai, Yan Lin* and Renhua Wu*,

{"title":"Visualization of Unconjugated Bilirubin In Vivo with a Novel Approach Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging in a Rat Model","authors":"Lin Yang, Yan Cheng, Yanlong Jia, Zhen Cao, Zerui Zhuang, Xiaolei Zhang, Jitian Guan, Rongzhi Cai, Yan Lin* and Renhua Wu*, ","doi":"10.1021/acschemneuro.4c0060410.1021/acschemneuro.4c00604","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00604https://doi.org/10.1021/acschemneuro.4c00604","url":null,"abstract":"Unconjugated bilirubin (UCB) visualization is valuable for early bilirubin encephalopathy (BE) diagnosis and management. UCB neurotoxicity is a challenge, necessitating improved imaging modalities for precise localization and characterization. This study developed a noninvasive method for UCB imaging in the brain using chemical exchange saturation transfer (CEST) magnetic resonance imaging, which visualizes UCB distribution through amide–bulk water proton exchange, a process termed bilirubin CEST (Bil-CEST) imaging. Bil-CEST imaging parameters were initially optimized; the exchange rate of the amide protons of UCB was calculated. Bil-CEST imaging characteristics and specificity were assessed using in vitro images of UCB solutions under different conditions and images of other brain metabolites. Bil-CEST maps of the rat brain were collected at the baseline and dynamically, postinjection of the UCB solution or vehicle into lateral ventricles of Sprague–Dawley rats. The model was validated using a water maze and pathological staining. In vitro, the Bil-CEST effect was observed at approximately 5.5 ppm downfield from bulk water. This effect was proportional to the UCB concentration and B1 amplitude. In vivo, Bil-CEST imaging revealed a progressive enhancement following a lateral ventricular UCB injection. Conversely, no significant imaging changes were observed in the vehicle group. Compared with the vehicle group, the UCB group had more hippocampal neuronal apoptosis and worse cognitive function. These findings highlight the utility of Bil-CEST in direct UCB imaging, indicating its potential as a clinically valuable biomarker for BE diagnosis and management.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4533–4543 4533–4543"},"PeriodicalIF":4.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142844158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0