Intracerebroventricular Treatment with 2-Hydroxypropyl-β-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann–Pick Disease Type C Model Mice
Abstract
:1. Introduction
2. Results
2.1. Protective Effects of Intracerebroventricular HP-β-CD Treatment on Neuronal Injury in Npc1-Deficient Mice
2.2. Evaluation of Soluble GPNMB (sGPNMB) Levels upon Intracerebroventricular HP-β-CD Treatment in Npc1−/− Mice
2.3. Attenuating Effect of Intracerebroventricular Injection of HP-β-CD on Abnormal Increases of GPNMB in Npc1−/− Mouse Cerebellum
2.4. Hepatoprotective Effects of Intracerebroventricular HP-β-CD Treatment in Npc1-Deficient Mice
2.5. Repeated Doses of Intracerebroventricular HP-β-CD Drastically Prolonged the Lifespan of Npc1-Deficient Mice
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Animal Experiments
4.2.1. Intracerebroventricular Administration of HP-β-CD in Npc1-Deficient Mice
4.2.2. Evaluation of Purkinje Cell Loss in the Cerebellum of Npc1-Deficient Mice
4.2.3. Quantification of GPNMB Levels of Npc1-Deficient Mice
4.2.4. Evaluation of Hepatic Changes in Npc1-Deficient Mice
4.2.5. Evaluation of Lifespan in Npc1-Deficient Mice
4.3. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
NPC | Niemann–Pick disease type C |
HP-β-CD | 2-Hydroxypropyl-β-cyclodextrin |
WT | Wild type |
ALT | Alanine aminotransferase |
AST | Aspartate aminotransferase |
H&E | Hematoxylin & eosin |
IU/L | International unit per liter |
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Fukaura, M.; Ishitsuka, Y.; Shirakawa, S.; Ushihama, N.; Yamada, Y.; Kondo, Y.; Takeo, T.; Nakagata, N.; Motoyama, K.; Higashi, T.; et al. Intracerebroventricular Treatment with 2-Hydroxypropyl-β-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann–Pick Disease Type C Model Mice. Int. J. Mol. Sci. 2021, 22, 452. https://doi.org/10.3390/ijms22010452
Fukaura M, Ishitsuka Y, Shirakawa S, Ushihama N, Yamada Y, Kondo Y, Takeo T, Nakagata N, Motoyama K, Higashi T, et al. Intracerebroventricular Treatment with 2-Hydroxypropyl-β-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann–Pick Disease Type C Model Mice. International Journal of Molecular Sciences. 2021; 22(1):452. https://doi.org/10.3390/ijms22010452
Chicago/Turabian StyleFukaura, Madoka, Yoichi Ishitsuka, Seiichi Shirakawa, Naoki Ushihama, Yusei Yamada, Yuki Kondo, Toru Takeo, Naomi Nakagata, Keiichi Motoyama, Taishi Higashi, and et al. 2021. "Intracerebroventricular Treatment with 2-Hydroxypropyl-β-Cyclodextrin Decreased Cerebellar and Hepatic Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Expression in Niemann–Pick Disease Type C Model Mice" International Journal of Molecular Sciences 22, no. 1: 452. https://doi.org/10.3390/ijms22010452