Article
Multidisciplinary Sciences
Lillian M. Toomey, Melissa Papini, Brittney Lins, Alexander J. Wright, Andrew Warnock, Terence McGonigle, Sarah C. Hellewell, Carole A. Bartlett, Chidozie Anyaegbu, Melinda Fitzgerald
Summary: The study showed that cuprizone pellets were more effective than cuprizone powder in inducing demyelinating disease pathology in mice, with better performance in certain indicators. However, both forms had similar effects on oligodendrocyte precursor cell dynamics.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Fuxing Dong, Dajin Liu, Feiyu Jiang, Yaping Liu, Xiuxiang Wu, Xuebin Qu, Jing Liu, Yan Chen, Hongbin Fan, Ruiqin Yao
Summary: The research indicates that Foxg1 plays a crucial role in the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) in demyelinating diseases. Foxg1 knockout decreases OPC proliferation and accelerates their differentiation into mature oligodendrocytes, possibly through regulation via the Wnt signaling pathway.
NEUROSCIENCE BULLETIN
(2021)
Article
Multidisciplinary Sciences
Fengmei Zheng, Yiqing Lin, Pierre Boulas
Summary: A hydrophilic interaction liquid chromatographic method was developed for the quantification of cuprizone in pre-clinical formulations, showing good specificity, linearity, and accuracy. The method was successfully applied to quantify low levels of cuprizone in chow formulations.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Yoshie Kawabe, Tatsuhide Tanaka, Ayami Isonishi, Kazuki Nakahara, Kouko Tatsumi, Akio Wanaka
Summary: Cells in the white matter of the adult brain form linear arrays called linear arrays (LAs), which are parallel to the axon axis. The presence of microglia is important for the characteristic cell localization pattern of LAs. Astrocytes are involved in maintaining the functions of remyelinated white matter.
NEUROCHEMICAL RESEARCH
(2022)
Article
Neurosciences
Marisa A. Jeffries, Lauren E. McLane, Luipa Khandker, Marie L. Mather, Angelina V. Evangelou, Divyangi Kantak, Jennifer N. Bourne, Wendy B. Macklin, Teresa L. Wood
Summary: This study investigated the role of mTOR signaling in oligodendrocyte lineage during remyelination. The results showed that mTOR is required for metabolic function in cuprizone-demyelinated adult brain, influencing myelin production efficiency and myelin thickness during the repair process. Loss of mTOR in OPCs did not affect remyelination efficiency after other types of lesions, suggesting a specific function in cuprizone-induced demyelination.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Anatomy & Morphology
S. H. El Sharouny, M. H. Shaaban, R. M. Elsayed, A. W. Tahef, M. K. Abd ElWahed
Summary: This study demonstrates the neuroprotective effects of N-acetylcysteine (NAC) in demyelinating diseases, particularly multiple sclerosis. Co-administration of cuprizone (CPZ) and NAC has a stronger protective impact compared to sequential administration. Prolonged CPZ administration delays spontaneous remyelination.
FOLIA MORPHOLOGICA
(2022)
Review
Biochemistry & Molecular Biology
Heinig Leo, Markus Kipp
Summary: Remyelination therapies are crucial in the treatment of multiple sclerosis, and the cuprizone model is a widely used model to study the effectiveness of new compounds. This review article summarizes recent findings using this model and discusses the potential of identified compounds in promoting remyelination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Xuesong Zhang, Johannes Weickenmeier
Summary: Brain maturation and neurological diseases are closely related to microstructural changes, which affect the brain's mechanical behavior. This study investigates stiffness changes in the brain due to demyelination using the cuprizone mouse model. The results show that there are region-specific stiffness changes in the corpus callosum, cingulum, and cortex. Fixation of the tissue also has a significant impact on stiffness and interregional stiffness ratios.
ACTA BIOMATERIALIA
(2023)
Article
Neurosciences
Akiko Uyeda, Lili Quan, Yuki Kato, Nagaaki Muramatsu, Shogo Tanabe, Kazuhisa Sakai, Noritaka Ichinohe, Yukio Kawahara, Tatsunori Suzuki, Rieko Muramatsu
Summary: Remyelination is a regenerative process that restores lost neurological function, partially dependent on oligodendrocyte differentiation. The study identified DDAH1 as a novel regulator of oligodendrocyte differentiation, with the potential to modulate remyelination in demyelinating diseases. Modulating DDAH1 activity could provide a new therapeutic option for demyelinating diseases.
Article
Neurosciences
Sarah Moyon, Mara Holloman, James L. L. Salzer
Summary: A major goal in demyelinating disease therapy is to improve remyelination. Progenitor cells and oligodendrocytes generated from neural stem cells (NSCs) are capable of forming new myelin sheaths. It is hypothesized that NSC-derived cells may compete with oligodendrocyte progenitor cells (pOPCs) to remyelinate the same axons, limiting the contribution of NSC-progeny. This study confirmed that pOPCs are the main remyelinating cells but NSC-derived cells are also activated and recruited to demyelinating lesions.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Yun Xiao, Yuan Zhang, Yu-Han Gao, Zhuo-Hua Zhao, Jin He, Rui Gao, Yu-Xin Guo, Li-Bin Wang, Xing Li
Summary: The main pathological characteristics of demyelinating diseases are CNS myelin damage and the differentiation of oligodendrocyte precursor cells plays a crucial role in myelin repair. Previous studies have shown that a large number of platelet-derived growth factor receptor a positive oligodendrocyte progenitor cells accumulate in the lesion area of myelin injury, but their differentiation is hindered. However, the therapeutic effects of currently used drugs on OPCs differentiation and myelin repair are limited. Efficiently delivering drugs to the CNS lesion area is of great significance for the treatment of multiple sclerosis. Natural exosomes, as ideal drug carriers with good biocompatibility, can be armed with targeting ligands to achieve drug delivery to the lesion areas. This study combines exosomes with PDGFA to help them accumulate in OPCs in vitro and in vivo, and load montelukast into exosomes for targeted therapy in a cuprizone-induced demyelination animal model. The implementation of this research will provide effective treatments for demyelinating diseases and lay a theoretical foundation for its clinical application in the treatment of different demyelinating diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Materials Science, Multidisciplinary
Yuting Yang, Jianwei Zhu, Wenjuan Ma, Wenqing Zhang, Yu Xie, Xingyu Chen, Junyao Zhu, Yuhao Liu, Xin Qin, Yunfeng Lin
Summary: Multiple sclerosis (MS) is a well-known demyelinating disease in young adults, lacking effective first-line drugs to delay progression and achieve clinical improvement. Tetrahedral framework nucleic acids (tFNAs) have shown positive effects on remyelination, potentially serving as a therapeutic approach for MS patients' disability.
APPLIED MATERIALS TODAY
(2021)
Article
Cell Biology
Pei-Lun Lai, Chi-Hou Ng, Chia-Hsin Wu, Chien-Ying Lai, Scott C. Schuyler, Vicki Wang, Hsuan Lin, Yueh-Chang Lee, Ming-Hsi Chuang, Chang-Huan Yang, Wei-Ju Chen, Hsiao-Chun Huang, Jean Lu
Summary: This study established an in vitro method to convert human fibroblasts into oligodendrocyte-like cells, and demonstrated that specific small molecules could induce the cells to acquire oligodendrocyte-like characteristics. By directly injecting these molecules into a mouse model of demyelination, the researchers successfully rescued the demyelination phenotype. These findings provide a foundation for the development of a remyelination therapy.
Article
Neurosciences
Nima Hasaniani, Maryam Ghasemi-Kasman, Mehrdad Halaji, Sahar Rostami-Mansoor
Summary: There is a bidirectional association between gut microbiota and central nervous system, which plays an important role in the pathophysiology of neurodegenerative disorders and regenerative processes. In this study, the effects of L. casei and B. breve on alternation performance, oxidant/antioxidant biomarkers, demyelination extent, and gene expression levels were investigated in a rat model of demyelination. The results showed that probiotics supplementation significantly improved alternation performance and antioxidant capacity, with B. breve being more effective in alleviating demyelination and oxidative stress levels.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Plant Sciences
Jinfeng Yuan, Nuo Xu, Yanlin Tao, Xinyan Han, Liu Yang, Jinglei Liang, Haojieyin Jin, Xiaoxia Zhang, Hui Wu, Hailin Shi, Fei Huang, Xiaojun Wu
Summary: This study found that total astragalosides (TA) can effectively enhance the differentiation and maturation of oligodendrocyte progenitor cells (OPCs) and accelerate remyelination in a mouse model of multiple sclerosis (MS). TA achieves this through inhibition of the Wnt/8-catenin signaling pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Neurosciences
Frank Y. Lee, Jennifer Larimore, Victor Faundez, Esteban C. Dell'Angelica, Cristina A. Ghiani
Summary: The absence of BLOC-1 during brain development affects male mice more than females, particularly in the hippocampus. While most abnormalities in juvenile animals seem to have been resolved, potential permanent defects may result in faulty neuronal circuits and contribute to cognitive and behavioral phenotypes in adult BLOC-1-deficient mice.
JOURNAL OF NEUROSCIENCE RESEARCH
(2021)
Article
Neurosciences
Mariapaola Sidoli, Chelsey B. Reed, Cristina Scapin, Pablo Paez, Douglas R. Cavener, Randal J. Kaufman, Maurizio D'Antonio, M. Laura Feltri, Lawrence Wrabetz
Summary: Despite the interaction between Perk and calcineurin in P0S63del nerves, Perk deletion paradoxically improved S63del myelin defects. Additionally, genetic manipulation of calcineurin subunits showed context-dependent protective or toxic effects in S63del, suggesting high sensitivity of Schwann cells to alterations in calcineurin activity.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Veronica T. Cheli, Diara A. Santiago Gonzalez, Qiuchen Wan, Giancarlo Denaroso, Rensheng Wan, Shaina L. Rosenblum, Pablo M. Paez
Summary: The storage of iron by astrocytes, particularly the Fth protein, is crucial for the early development of oligodendrocytes and the remyelination of the central nervous system. Knocking out Fth in astrocytes led to delays in oligodendrocyte development and myelin synthesis, as well as a decrease in the number of myelinating oligodendrocytes and the percentage of myelinated axons. These findings suggest that astrocytic iron storage plays a vital role in the myelination process and repair of myelin damage.
Article
Biochemistry & Molecular Biology
D. A. Santiago Gonzalez, V. T. Cheli, S. L. Rosenblum, G. Denaroso, P. M. Paez
Summary: Ceruloplasmin is an essential ferroxidase enzyme for cell iron efflux and plays a crucial role in promoting the maturation of OLs and SCs by regulating iron balance and preventing oxidative stress and neurodegeneration in the central and peripheral nervous systems.
Article
Cardiac & Cardiovascular Systems
Saemi Park, Shu Hon Christopher Luk, Raj S. Bains, Daniel S. Whittaker, Emily Chiem, Maria C. Jordan, Kenneth P. Roos, Cristina A. Ghiani, Christopher S. Colwell
Summary: Reducing mHTT expression in the heart benefits cardiovascular function and alleviates pathological cardiac hypertrophy and fibrosis in a Huntington's disease model.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Nutrition & Dietetics
Daniel S. Whittaker, T. Katherine Tamai, Raj S. Bains, Sophia Anne Marie Villanueva, Shu Hon Christopher Luk, Derek Dell'Angelica, Gene D. Block, Cristina A. Ghiani, Christopher S. Colwell
Summary: This study focuses on disturbances in sleep/wake cycles in Huntington's disease (HD) and investigates the effects of a low-carbohydrate, high-fat diet on HD progression using a mouse model. The results show that the diet improves sleep quality and delays disease progression in the mice. Additionally, the diet has transcriptional effects in the brain and affects the microbiome.
FRONTIERS IN NUTRITION
(2022)
Article
Neurosciences
Huei-Bin Wang, David Zhou, Shu Hon Christopher Luk, Hye In Cha, Amanda Mac, Rim Chae, Anna Matynia, Ben Harrison, Sina Afshari, Gene D. Block, Cristina A. Ghiani, Christopher S. Colwell
Summary: Many patients with autism spectrum disorders (ASD) have disrupted sleep/wake cycles and may be more vulnerable to the effects of circadian disruptors. Previous research has shown that exposure to dim light at night (DLaN) for 2 weeks disrupts diurnal rhythms, increases repetitive behaviors, and reduces social interactions. This study found that shifting the DLaN stimulus to longer wavelengths mitigated the negative impact on activity rhythms and 'autistic' behaviors in both neurotypical and vulnerable populations. These findings highlight the importance of considering the spectral properties of light at night for optimizing health.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
V. T. Cheli, M. Sekhar, D. A. Santiago Gonzalez, C. G. Angeliu, G. E. Denaroso, Z. Smith, C. Wang, P. M. Paez
Summary: Ceruloplasmin (Cp) is crucial for cell iron efflux and its absence leads to neurodegeneration and brain iron accumulation. This study found that astrocytes express high levels of Cp and its iron efflux is essential for oligodendrocyte maturation and myelination. Deletion of astrocytic Cp during early postnatal stages resulted in hypomyelination, delayed oligodendrocyte maturation, and increased oxidative stress. Deletion of astrocytic Cp in older mice led to iron accumulation, neurodegeneration, myelin loss, and abnormal behavioral profiles. The study highlights the importance of astrocytic Cp in brain development, aging, and myelin integrity.
Article
Neurosciences
Veronica T. Cheli, Diara A. Santiago Gonzalez, Rensheng Wan, Shaina L. Rosenblum, Giancarlo E. Denaroso, Christina G. Angeliu, Zachary Smith, Congying Wang, Pablo M. Paez
Summary: By disrupting the expression of the Tf receptor gene in oligodendrocyte progenitor cells, researchers found that the Tf cycle is uniquely important for the development and function of oligodendrocytes. Deleting the Tfr gene resulted in impaired iron absorption and hypomyelination in mice. The Tf cycle plays a crucial role in iron homeostasis and energy production in oligodendrocyte progenitor cells.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Immunology
G. E. Denaroso, Z. Smith, C. G. Angeliu, V. T. Cheli, C. Wang, P. M. Paez
Summary: In this study, the role of astrocytic voltage-gated Ca++ channels in autoimmune inflammation and demyelination in the central nervous system (CNS) was investigated using the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis combined with Cav1.2 conditional knock-out mice. The results showed that deleting Cav1.2 channels in astrocytes significantly reduced the severity of the disease and protected the spinal cord from autoimmune demyelination.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Jeffrey L. Dupree, Pablo M. Paez, Seema K. Tiwari-Woodruff, Travis T. Denton, Kenneth Hensley, Christina G. Angeliu, Anne Boullerne, Sergey Kalinin, Sophia Egge, Veronica T. Cheli, Giancarlo Denaroso, Kelley C. Atkinson, Micah Feri, Douglas L. Feinstein
Summary: The study shows that lanthionine ketenamine ethyl ester (LKE) can increase remyelination and promote the maturation of oligodendrocyte progenitor cells (OPCs) in a mouse model. This suggests that LKE may have potential therapeutic effects in neurological diseases associated with demyelination, such as multiple sclerosis (MS).