Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration
Abstract
:1. Introduction
2. Results
2.1. Increased PLD1 Levels and Increased Co-Localization with Amyloidogenic Proteins in Post-Mortem Human AD Hippocampal Slices Compared to Age-Matched Control
2.2. Chronic One-Month Treatment with PLD1 Inhibitor (VU0155069 or VU01 at 1 mg/kg/2 Days i.p.) in 12-Month-Old 3xTg-AD Mice Attenuates PLD1, PLD1-Aβ and PLD1-tau Co-Staining Expression Differentially in Hippocampal Subregions
2.3. VU01 Dependent Chronic Inhibition of PLD1 Preserves Specific Dendritic Spine Morphologies in 12-Month-Old 3xTg-AD Mice
2.4. Restoration of Hippocampal Synaptic Function by Chronic PLD1 Inhibition Regimen in 12-Month-Old 3xTg-AD Mice
2.5. Chronic One-Month Treatment with PLD1 Inhibitor Ameliorates Memory Deficits in 12-Month-Old 3xTg-AD Mice
3. Discussion
4. Materials and Methods
4.1. Drugs
4.2. Human Samples
4.3. Animals
4.4. Field Electrophysiological Recordings
4.5. Behaviors
4.5.1. Novel Object Recognition
4.5.2. Fear Conditioned Response
4.6. Tissue Processing and Golgi–Cox Staining
4.7. Dendrite Imaging
4.8. Immunofluorescence
4.9. Quantitative Microscopy
4.10. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Case No. | Diagnosis | Age (Years) | Gender | Braak Stage | MMSE | PMI (h) |
---|---|---|---|---|---|---|
1220 | CTRL | >89 | F | 2 | 30 | 12 |
2467 | CTRL | 99 | F | 3 | 28 | 4.5 |
2553 | CTRL | 100 | M | 2 | 28 | 4 |
2682 | CTRL | 90 | F | 2 | 29 | 9 |
2755 | CTRL | 95 | F | 2 | 29 | 18 |
2953 | CTRL | 100 | F | 3 | 27 | 2.5 |
1678 | AD | 76 | F | 6 | 1 | 25 |
2312 | AD | 87 | F | 6 | - | 2.5 |
2316 | AD | 83 | M | 5 | - | 13 |
2317 | AD | 88 | M | 6 | - | 4 |
2374 | AD | 91 | M | 6 | - | 24 |
2543 | AD | 95 | M | 6 | 21 | 5 |
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Natarajan, C.; Cook, C.; Ramaswamy, K.; Krishnan, B. Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration. Int. J. Mol. Sci. 2023, 24, 3372. https://doi.org/10.3390/ijms24043372
Natarajan C, Cook C, Ramaswamy K, Krishnan B. Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration. International Journal of Molecular Sciences. 2023; 24(4):3372. https://doi.org/10.3390/ijms24043372
Chicago/Turabian StyleNatarajan, Chandramouli, Charles Cook, Karthik Ramaswamy, and Balaji Krishnan. 2023. "Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration" International Journal of Molecular Sciences 24, no. 4: 3372. https://doi.org/10.3390/ijms24043372
APA StyleNatarajan, C., Cook, C., Ramaswamy, K., & Krishnan, B. (2023). Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration. International Journal of Molecular Sciences, 24(4), 3372. https://doi.org/10.3390/ijms24043372