The Dual PDE7-GSK3β Inhibitor, VP3.15, as Neuroprotective Disease-Modifying Treatment in a Model of Primary Progressive Multiple Sclerosis
Abstract
:1. Introduction
2. Results
2.1. The PDE7/GSK3 Dual Inhibitor VP3.15 Ameliorates Motor Function of TMEV-IDD
2.2. VP3.15 Limits Microglial Activation and Lymphocyte Infiltration in the Spinal Cord of TMEV Infected Mice
2.3. The Remyelinating Role of VP3.15 and Its Effect in the Integrity of Axons of TMEV Mice
2.4. VP3.15 Promotes the Presence of Mature Oligodendrocytes in Spinal Cord
3. Discussion
4. Materials and Methods
4.1. Animal and Theiler’s Virus Inoculation
4.2. Treatments and Evaluation of Motor Function
4.3. Tissue Processing
4.4. Eriochrome Cyanine Staining
4.5. Immunofluorescence Analysis
4.6. Immunohistochemistry Analysis
4.7. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antibody | Target | Cellular Location | Dilution | Host Species | Class | Manufacturer | Antibody ID |
---|---|---|---|---|---|---|---|
MBP | Myelin | Plasma Membrane | 1:500 | Rat | Monoclonal clone 12 | Biorad | aa 82–87 |
NFH | Neurons/ Axons | Cell Body | 1:1000 | Rabbit | Polyclonal | Abcam | Ab 8135 |
Iba-1 | Microglia | Plasma membrane | 1:500 | Guinea pig | Polyclonal | Synaptic Systems | 234 004 |
PDGFRα | OPCs | Plasma membrane | 1:200 | Goat | Polyclonal | RD Systems | AF 1062 |
CC1 | Mature oligodendrocytes | Cell body | 1:200 | Mouse | Monoclonal clone CC1 | Merck Millipore | OP 80 |
Olig2 | Oligodendrocyte lineage | Nucleus | 1:200 | Rabbit | Polyclonal | Merck Millipore | AB 9610 |
CD4 | T cell | Plasma membrane | 1:250 | Rat | Monoclonal | BD Pharmingen | 550278 |
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Benítez-Fernández, R.; Gil, C.; Guaza, C.; Mestre, L.; Martínez, A. The Dual PDE7-GSK3β Inhibitor, VP3.15, as Neuroprotective Disease-Modifying Treatment in a Model of Primary Progressive Multiple Sclerosis. Int. J. Mol. Sci. 2022, 23, 14378. https://doi.org/10.3390/ijms232214378
Benítez-Fernández R, Gil C, Guaza C, Mestre L, Martínez A. The Dual PDE7-GSK3β Inhibitor, VP3.15, as Neuroprotective Disease-Modifying Treatment in a Model of Primary Progressive Multiple Sclerosis. International Journal of Molecular Sciences. 2022; 23(22):14378. https://doi.org/10.3390/ijms232214378
Chicago/Turabian StyleBenítez-Fernández, Rocio, Carmen Gil, Carmen Guaza, Leyre Mestre, and Ana Martínez. 2022. "The Dual PDE7-GSK3β Inhibitor, VP3.15, as Neuroprotective Disease-Modifying Treatment in a Model of Primary Progressive Multiple Sclerosis" International Journal of Molecular Sciences 23, no. 22: 14378. https://doi.org/10.3390/ijms232214378