Early Effects of the Soluble Amyloid β25-35 Peptide in Rat Cortical Neurons: Modulation of Signal Transduction Mediated by Adenosine and Group I Metabotropic Glutamate Receptors
Abstract
:1. Introduction
2. Results
2.1. Characterization of Aβ-Induced Toxicity on Cortical Neurons
2.2. Aβ25-35 Exposure Effect on the Density and Affinity of Metabotropic Glutamate Receptors
2.3. Aβ25-35 Effect on Group I Metabotropic Glutamate Receptors’ Gene Expression and Protein Levels
2.4. Modulation of PLC β1 Signalling Pathway after Aβ25-35 Exposure
2.5. Effect of Aβ25-35 Exposure on Metabotropic Glutamate Receptors/Adenylyl Cyclase Pathway
2.6. Effect of Aβ25-35 Exposure on Adenosine A1 and A2A Receptors
2.7. Effect of Aβ25-35 Exposure on Adenosine Receptor Gene Expression
2.8. Effect of Aβ25-35 Exposure on Adenosine Receptors-Mediated Adenylyl Cyclase Activity
2.9. Effect of Aβ25-35 Exposure on the Expression of Genes Coding for CREB and CREM
2.10. Effect of Group I Metabotropic Glutamate and Adenosine A1 and A2A Receptors Ligands on Aβ25-35 Induced Toxicity
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Primary Culture of Cortical Neurons
4.3. Drug Treatments and Evaluation of Cell Death
4.4. Caspase 3 Activity Assay
4.5. Quantification of Metabotropic Glutamate and Adenosine Receptors in Intact Cells by Radioligand Binding Assay
4.6. Extracellular Targeting of mGluR1, mGluR5 and mGluR2,3 by Immunochemistry
4.7. PLCβ1 Immunocytochemistry
4.8. Microscopy Imaging
4.9. Determination of Phospholipase C Activity
4.10. Determination of Adenylyl Cyclase Activity
4.11. Preparation of Total RNA and cDNA
4.12. Quantitative Real-Time RT-PCR Analysis
4.13. Protein Determination
4.14. Statistics and Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Control | Aβ25-35 24 h | Aβ25-35 48 h | |
Total mGluR | |||
Bmax (pmol/mg prot) | 590 ± 31 | 952 ± 9 ** | 1178 ± 93 *** |
KD (µM) | 3.069 ± 0.062 | 1.607 ± 0.423 ** | 1.522 ± 0.163 ** |
A1R | |||
Bmax (fmol/mg prot) | 149 ± 6 | 545 ± 101 ** | 423 ± 66 * |
KD (nM) | 1.16 ± 0.16 | 7.51 ± 2.35 * | 5.51 ± 1.33 * |
A2AR | |||
Bmax (fmol/mg prot) | 656 ± 51 | 557 ± 56 | 1178 ± 43 *** |
KD (nM) | 13.26 ± 0.26 | 10.33 ± 1.22 | 13.96 ± 4.69 |
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Castillo, C.A.; Ballesteros-Yáñez, I.; León-Navarro, D.A.; Albasanz, J.L.; Martín, M. Early Effects of the Soluble Amyloid β25-35 Peptide in Rat Cortical Neurons: Modulation of Signal Transduction Mediated by Adenosine and Group I Metabotropic Glutamate Receptors. Int. J. Mol. Sci. 2021, 22, 6577. https://doi.org/10.3390/ijms22126577
Castillo CA, Ballesteros-Yáñez I, León-Navarro DA, Albasanz JL, Martín M. Early Effects of the Soluble Amyloid β25-35 Peptide in Rat Cortical Neurons: Modulation of Signal Transduction Mediated by Adenosine and Group I Metabotropic Glutamate Receptors. International Journal of Molecular Sciences. 2021; 22(12):6577. https://doi.org/10.3390/ijms22126577
Chicago/Turabian StyleCastillo, Carlos Alberto, Inmaculada Ballesteros-Yáñez, David Agustín León-Navarro, José Luis Albasanz, and Mairena Martín. 2021. "Early Effects of the Soluble Amyloid β25-35 Peptide in Rat Cortical Neurons: Modulation of Signal Transduction Mediated by Adenosine and Group I Metabotropic Glutamate Receptors" International Journal of Molecular Sciences 22, no. 12: 6577. https://doi.org/10.3390/ijms22126577