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8. CEST imaging combined with 1H-MRS reveal the neuroprotective effects of riluzole by improving neurotransmitter imbalances in Alzheimer's disease mice.

Author

Shen, Yuanyu, Zhang, Xiaolei, Liu, Siqi, Xin, Lijing, Xuan, Wentao, Zhuang, Caiyu, Chen, Yue, Chen, Beibei, Zheng, Xinhui, Wu, Renhua, and Lin, Yan

Subjects
PROTON magnetic resonance spectroscopy, GLUTAMATE decarboxylase, EXCITATORY amino acids, ALZHEIMER'S disease, AMYOTROPHIC lateral sclerosis
Abstract

Background: The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitter system plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Riluzole is a Glu modulator originally approved for amyotrophic lateral sclerosis that has shown potential neuroprotective effects in various neurodegenerative disorders. However, whether riluzole can improve Glu and GABA homeostasis in AD brain and its related mechanism of action remain unknown. This study utilized chemical exchange saturation transfer (CEST) imaging combined with proton magnetic resonance spectroscopy (1H-MRS) to monitor the dynamic changes of Glu and GABA in riluzole-treated AD mice, aiming to evaluate the efficacy and mechanism of riluzole in AD treatment. Methods: GluCEST, GABACEST and 1H-MRS were used to longitudinally monitor Glu and GABA levels in 3xTg AD mice treated with riluzole (12.5 mg/kg/day) or vehicle for 20 weeks. Magnetic resonance measurements were performed at baseline, 6, 12, and 20 weeks post-treatment. Cognitive performance was assessed using the Morris Water Maze (MWM) at baseline, 10, and 20 weeks. At the study endpoint, immunohistochemistry, Nissl staining, and Western blot were used to evaluate the brain pathology, neuronal survival, and protein expression. Results: GluCEST, GABACEST and 1H-MRS consistently revealed higher levels of Glu and GABA in the brain of riluzole-treated AD mice compared to untreated controls, which were associated with improvements in spatial learning and memory. The cognitive improvements significantly correlated with the increased GluCEST signals and Glu levels. Immunohistochemistry and Nissl staining demonstrated that riluzole treatment reduced amyloid-beta (Aβ) deposition, tau hyperphosphorylation, GFAP-positive astrocyte activation, and prevented neuronal loss. Moreover, riluzole upregulated the expression of excitatory amino acid transporter 2 (EAAT2), glutamic acid decarboxylase 65/67 (GAD65/67), and glutamine synthetase (GS), suggesting enhanced neurotransmitter metabolism. Conclusions: CEST imaging combined with 1H-MRS demonstrated the effectiveness of riluzole in modulating Glu- and GABA-related changes and improving cognitive function in 3xTg AD mice, potentially through regulating key proteins involved in neurotransmitter metabolism. These findings suggest riluzole as a therapeutic agent for Alzheimer's disease and highlight the utility of multimodal MR imaging in monitoring treatment response and exploring disease mechanisms. [ABSTRACT FROM AUTHOR]

Published
2025
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10. Early Alzheimer's disease diagnosis via handwriting with self-attention mechanisms.

Author

Kang, Lei, Zhang, Xiaolei, Guan, Jitian, Huang, Kai, and Wu, Renhua

Subjects
MAGNETIC resonance imaging, GRAPHOLOGY, ALZHEIMER'S disease, CONVOLUTIONAL neural networks, DEEP learning
Abstract

Background: The neurodegenerative diseases like Alzheimer's disease (AD) can result in progressive decline in both cognitive functions and motor skills, which have critical need for accurate early diagnosis. However, current diagnosis approaches primarily rely on timely clinical magnetic resonance imaging (MRI) scans, which impede widely application for potential patients. Leveraging handwriting as a diagnostic tool offers significant potential for identifying AD in its early stages. Objective: This study aims to develop an efficient, rapid, and accurate method for early diagnosis of AD by utilizing handwriting analysis, a promising avenue due to its association with compromised motor skills in neurodegenerative diseases. Methods: We propose a novel methodology that leverages self-attention mechanisms for the early diagnosis of AD. Our approach integrates data from 25 distinct handwriting tasks available in the DARWIN (Diagnosis AlzheimeR WIth haNdwriting) dataset. Results: The Self-Attention model achieved an accuracy of 94.3% and an F1-score of 94.5%, outperforming other state-of-the-art models, including traditional machine learning and deep learning approaches. Specially, the Self-Attention model surpassed the previous best model, the convolutional neural networks, by approximately 4% in both accuracy and F1-score. Additionally, the model demonstrated superior precision (94.7%), sensitivity (94.5%), and specificity (94.1%), indicating high reliability and excellent identification of true positive and true negative cases, which is crucial in medical diagnostics. Conclusions: Handwriting analysis, powered by self-attention mechanisms, offers significant potential as a diagnostic tool for identifying AD in its early stages, providing an effective alternative to traditional MRI-based diagnosis. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Five percent CO2inhalation alleviates hippocampal glutamate and water homeostasis disturbance, neuronal damage, and learning‐memory impairment in sleep‐deprived rats

Author

Zhao, Zhihong, Zhang, Xiaojun, Zhang, Xiaolei, Xie, Shiyan, Chen, Yue, Lai, Lingfeng, Xin, Lijing, Guan, Jitian, Lin, Yan, and Wu, Renhua

Abstract

Sleep deprivation causes hippocampal injury, manifesting as neuronal damage and learning‐memory impairment. These negative effects may be associated with disturbance of hippocampal glutamate and water homeostasis, which induces excessive neuronal excitability. Five percent CO2inhalation has been shown to suppress neuronal excitability. Here, we aimed to investigate whether 5% CO2inhalation facilitates the recovery of hippocampal glutamate and water homeostasis, neuron morphology, and learning‐memory ability in sleep‐deprived rats. Thirty‐six Sprague‐Dawley female rats were randomly divided into three groups including normal sleep (Group 1, NS, n= 12), sleep deprivation followed by sleep recovery (Group 2, SD+SR, n= 12), sleep deprivation followed by sleep recovery and 5% CO2inhalation (Group 3, SD+SR+CO2, n= 12) by random number table. Each group was divided into two subgroups (n= 6 each subgroup) for different experiments randomly by random number table. We found that 5% CO2inhalation facilitated the recovery of hippocampal glutamate concentration (7.549 ± 0.310, 8.716 ± 0.463, and 7.493 ± 0.281 mmol/L at Days 1, 3, and 5 in Group 3, F2, 15= 22.06, p< 0.0001) and hippocampal apparent diffusion coefficient mean value (8.210 ± 0.274, 7.685 ± 0.171, 8.265 ± 0.269 at Days 1, 3, and 5 in Group 3, F2, 15= 10.45, p= 0.0014), enhanced expression level of astrocyte‐specific membrane protein glutamate transporter‐1, promoted the polarized distribution of aquaporin 4, reduced hippocampal neuronal damage and improved learning‐memory ability in sleep‐deprived rats. This study showed that 5% CO2inhalation can serve as a novel strategy for alleviating sleep deprivation‐induced hippocampal injury. Five percent CO2inhalation alleviates hippocampal glutamate and water homeostasis disturbance, neuronal damage, and learning‐memory impairment in sleep‐deprived rats. Five percent CO2inhalation promotes the recovery of glutamate concentration and water diffusion, increases the level of excitatory amino acid transporter 2 and promotes the polarization of aquaporin 4 in the hippocampi of sleep‐deprived rats.Five percent CO2inhalation decreases hippocampal neuronal injury in sleep‐deprived rats.Five percent CO2inhalation promotes learning‐memory ability in sleep‐deprived rats. Five percent CO2inhalation promotes the recovery of glutamate concentration and water diffusion, increases the level of excitatory amino acid transporter 2 and promotes the polarization of aquaporin 4 in the hippocampi of sleep‐deprived rats. Five percent CO2inhalation decreases hippocampal neuronal injury in sleep‐deprived rats. Five percent CO2inhalation promotes learning‐memory ability in sleep‐deprived rats.

Published
2024
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35. Enzyme-free photothermally amplified fluorescent immunosorbent assay (PAFISA) for sensitive cytokine quantification

Author

Li, Dian, He, Wei, Lin, Xuyan, Cui, Xiaodong, Nagl, Stefan, Wu, Angela Ruohao, Kwok, Ryan T. K., Wu, Renhua, Tang, Benzhong, Li, Dian, He, Wei, Lin, Xuyan, Cui, Xiaodong, Nagl, Stefan, Wu, Angela Ruohao, Kwok, Ryan T. K., Wu, Renhua, and Tang, Benzhong

Abstract

Cytokine monitoring has attracted great attention due to its significance in the diagnosis and treatment of many diseases, such as tumors, microbial infections, and immunological diseases. Enzyme-linked immunosorbent assay (ELISA) is one of the most popular methods in cytokine detection, ascribing to the lavish signal amplification methods in the ELISA platform. In addition to classical enzymes, other signal amplifiers such as fluorescent probes, artificial nano-enzymes, and photothermal reagents have been applied to reduce the detection limit and produce more sensitive ELISA kits. Due to the accumulative effect of heat, photothermal reagents are promising materials in the signal amplification of ELISA. However, the lack of efficient photothermal generation material at an aggregate scale may delay the further development of this area. In this contribution, based on an efficient organic photothermal aggregate material, an enzyme-free photothermally amplified fluorescent immunosorbent assay system consisting of an assay microfluidic chip and detecting platform was developed. The photothermal nanoparticles with highly efficient photothermal conversion by harvesting energy via excited-state intramolecular motions and enlarging molar absorptivity were successfully prepared. The detection concentration at 50 pg/mL of interleukin-2 was achieved, realizing a signal improvement of detection limits by 20-fold compared to that of previously reported photothermal ELISA. The microscopic imaging integrated with plane sweeping technology provided high spatial resolution and precision, indicating the potential of achieving high throughput profiling at the microscale. Moreover, as an alternative excitation source, light-emitting diode not only provided a more affordable and miniaturized detection system but also revealed the great feasibility of intramolecular motion-induced photothermy nanoparticles for biological analyses. © 2023 The Authors. Aggregate published by SCUT, AIEI, and

Published
2023

48. Amide Proton Transfer-Weighted Imaging Detects Hippocampal Proteostasis Disturbance Induced by Sleep Deprivation at 7.0 T MRI

Author

Zhao, Zhihong, primary, Zhang, Xiaojun, additional, Zhang, Xiaolei, additional, Cheng, Yan, additional, Chen, Lihua, additional, Shen, Zhiwei, additional, Chen, Beibei, additional, Wang, Hongzhi, additional, Chen, Yue, additional, Xuan, Wentao, additional, Zhuang, Zerui, additional, Zheng, Xinhui, additional, Geng, Yiqun, additional, Dong, Geng, additional, Guan, Jitian, additional, Lin, Yan, additional, and Wu, Renhua, additional

Published
2022
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49. Automated detection of intracranial artery stenosis and occlusion in magnetic resonance angiography: A preliminary study based on deep learning

Author

Qiu, Jinming, primary, Tan, Guanru, additional, Lin, Yan, additional, Guan, Jitian, additional, Dai, Zhuozhi, additional, Wang, Fei, additional, Zhuang, Caiyu, additional, Wilman, Alan H., additional, Huang, Huaidong, additional, Cao, Zhen, additional, Tang, Yanyan, additional, Jia, Yanlong, additional, Li, Yan, additional, Zhou, Teng, additional, and Wu, Renhua, additional

Published
2022
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