Regulation of Neuronal Chloride Homeostasis by Pro- and Mature Brain-Derived Neurotrophic Factor (BDNF) via KCC2 Cation–Chloride Cotransporters in Rat Cortical Neurons
Abstract
:1. Introduction
2. Results
2.1. Functional Activity of KCC2 and BDNF Signaling Pathways in Maturing Cultured Hippocampal Neurons
2.2. proBDNF Maintains a Depolarized GABA Response in Hippocampal Neurons
2.3. Effects of Pro- and Mature-BDNF on KCC2 Cell Trafficking
2.4. KCC2-Dependent Ammonium Transport in BDNF-Treated Hippocampal Neurons
2.5. CR-proBDNF-Electroporated Rat Pups Exhibited Behavioral Deficits
2.6. CR-proBDNF-Electroporated Rats Exhibited Deficits in Sensory–Motor Maturation
3. Discussion
4. Materials and Methods
4.1. Reagents and Treatments
4.2. Primary Cultures of Rat Hippocampal Neurons
4.3. Transfections
4.4. NH+4 Flux Assay
4.5. Gramicidin-Perforated Patch-Clamp Recordings
4.6. Immunocytochemistry and Confocal Microscopy
4.7. Surface Immunolabeling on Living Neurons and Analysis of KCC2-pHext Proteins
4.8. In Utero Electroporation
4.9. Developmental Landmarks and Behavioral Tests
4.10. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Days/Condition | GFP | CR-proBDNF | BDNF |
---|---|---|---|
2 | 0.16 ± 0.37 | 0.23 ± 0.57 | 0.18 ± 0.55 |
3 | 0.44 ± 0.67 | 0.1 ± 0.4 * | 0.21 ± 0.57 |
4 | 0.63 ± 0.7 | 0.4 ± 0.72 | 0.61 ± 0.88 |
5 | 0.94 ± 0.88 | 0.63 ± 0.85 | 1.54 ± 0.74 # |
6 | 1.56 ± 0.76 | 0.7 ± 0.92 *** | 1.5 ± 0.79 $$ |
7 | 1.84 ± 0.45 | 1.03 ± 0.93 *** | 1.82 ± 0.48 $$$ |
8 | 1.94 ± 0.25 | 1.43 ± 0.82 ** | 1.9 ± 0.31 $ |
9 | 1.91 ± 0.3 | 1.6 ± 0.62 * | 1.93 ± 0.26 $$ |
10 | 1.97 ± 0.18 | 1.7 ± 0.66 * | 2 ± 0 $$ |
11 | 1.88 ± 0.34 | 1.9 ± 0.4 | 1.93 ± 0.26 |
12 | 2 ± 0 | 2 ± 0 | 2 ± 0 |
13 | 2 ± 0 | 2 ± 0 | 2 ± 0 |
14 | 2 ± 0 | 2 ± 0 | 2 ± 0 |
15 | 2 ± 0 | 2 ± 0 | 2 ± 0 |
Days/Condition | GFP | CR-proBDNF | BDNF |
---|---|---|---|
2 | 30 ± 0 | 28.7 ± 5.08 | 28.96 ± 4.31 |
3 | 28 ± 6.37 | 29.6 ± 2.37 | 28.54 ± 5.39 |
4 | 27.53 ± 6.7 | 28.23 ± 4.75 | 25.54 ± 8.24 |
5 | 24.5 ± 8.67 | 26.03 ± 7.62 | 17.5 ± 9.68 $$ # |
6 | 17.4 ± 9.23 | 24.9 ± 8.79 ** | 18.54 ± 10.11 |
7 | 15.16 ± 8.15 | 24.3 ± 7.95 *** | 17.64 ± 8.63 $ |
8 | 12.78 ± 7.51 | 19.4 ± 9.77 * | 12.61 ± 8.45 $ |
9 | 13.5 ± 7.93 | 21.03 ± 10.16 * | 10.18 ± 7.65 $$$$ |
10 | 8.7 ± 6.3 | 17.5 ± 8.95 **** | 7.71 ± 4.31 $$$$ |
11 | 9.31 ± 8.59 | 13 ± 7.27 ** | 9.5 ± 7.71 $ |
12 | 4.9 ± 3.07 | 9.83 ± 6.74 **** | 5.32 ± 2.68 $$ |
13 | 4.4 ± 2.47 | 5.3 ± 3.01 | 4.14 ± 2.37 |
14 | 3.31 ± 1.18 | 4.4 ± 3.78 | 2.9 ± 1.75 $ |
15 | 2.63 ± 1.16 | 4.23 ± 3.45 | 2.11 ± 0.95 $$ |
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Hamze, M.; Brier, C.; Buhler, E.; Zhang, J.; Medina, I.; Porcher, C. Regulation of Neuronal Chloride Homeostasis by Pro- and Mature Brain-Derived Neurotrophic Factor (BDNF) via KCC2 Cation–Chloride Cotransporters in Rat Cortical Neurons. Int. J. Mol. Sci. 2024, 25, 6253. https://doi.org/10.3390/ijms25116253
Hamze M, Brier C, Buhler E, Zhang J, Medina I, Porcher C. Regulation of Neuronal Chloride Homeostasis by Pro- and Mature Brain-Derived Neurotrophic Factor (BDNF) via KCC2 Cation–Chloride Cotransporters in Rat Cortical Neurons. International Journal of Molecular Sciences. 2024; 25(11):6253. https://doi.org/10.3390/ijms25116253
Chicago/Turabian StyleHamze, Mira, Cathy Brier, Emmanuelle Buhler, Jinwei Zhang, Igor Medina, and Christophe Porcher. 2024. "Regulation of Neuronal Chloride Homeostasis by Pro- and Mature Brain-Derived Neurotrophic Factor (BDNF) via KCC2 Cation–Chloride Cotransporters in Rat Cortical Neurons" International Journal of Molecular Sciences 25, no. 11: 6253. https://doi.org/10.3390/ijms25116253