Memantine and the Kynurenine Pathway in the Brain: Selective Targeting of Kynurenic Acid in the Rat Cerebral Cortex
Abstract
:1. Introduction
2. Materials and Methods
2.1. Experimental Protocol
2.2. Brain Levels of Kynurenines
2.3. Enzymatic Analyses of Semi-Purified Kynurenine Aminotransferases (KAT I and II)
2.4. Quantification of Tryptophan, L-Kynurenine, and Kynurenic Acid in Brain Samples
2.5. Quantification of 3-Hydroxykynurenine in Brain Samples
2.6. Statistical Analyses
3. Results
3.1. The Influence of Acute and 5-Day Administration of Memantine on the Content of Kynurenic Acid, Kynurenine, Tryptophan, and 3-HK in the Cortex
3.2. The Influence of Acute and 5-Day Administration of Memantine on the Content of Kynurenic Acid, Kynurenine, Tryptophan, and 3-HK in the Hippocampus
3.3. The Influence of Acute and 5-Day Administration of Memantine on the Content of Kynurenic Acid, Kynurenine, Tryptophan, and 3-HK in the Striatum
3.4. The Influence of Acute and 5-Day Administration of Memantine on the Content of Kynurenic Acid, Kynurenine, Tryptophan, and 3-HK in the Cerebellum
3.5. The Effects of Acute and 5-Day Administration of Memantine on the Cortical Activity of Semi-Purified Kynurenine Aminotransferases I and II
3.6. The Influence of Memantine on TRP/KYN, KYN/KYNA, KYN/3-HK, and KYNA/3-HK Ratios
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Brain Structure | Ratio | Control | Memantine |
---|---|---|---|
Cortex | TRP/L-KYN | 28.28 ± 2.41 | 29.29 ± 2.68 |
TRP/KYNA | 927.36 ± 250.71 | 838.35 ± 168.35 | |
L-KYN/KYNA | 32.80 ± 8.93 | 28.18 ± 4.48 | |
3-HK/KYNA | 1.79 ± 1.21 | 1.55 ± 0.4 | |
L-KYN/3-HK | 26.71 ± 19.69 | 18.88 ± 3.57 | |
TRP/3-HK | 749.31 ± 532.23 | 563.15 ± 119.93 | |
Striatum | TRP/L-KYN | 3.07 ± 0.56 | 3.03 ± 0.48 |
TRP/KYNA | 149.40 ± 37.36 | 123.73 ± 45.27 | |
L-KYN/KYNA | 48.76 ± 12.14 | 41.74 ± 18.38 | |
3-HK/KYNA | 10.02 ± 3.36 | 8.66 ± 3.48 | |
L-KYN/3-HK | 5.48 ± 2.77 | 4.93 ± 1.34 | |
TRP/3-HK | 15.84 ± 4.52 | 14.64 ± 3.46 | |
Hippocampus | TRP/L-KYN | 131.98 ± 100.98 | 82.62 ± 33.85 |
TRP/KYNA | 5730.12 ± 631.82 | 3453.57 ± 768.65 | |
L-KYN/KYNA | 51.58 ± 36.51 | 48.92 ± 22.79 | |
3-HK/KYNA | 0.18 ± 0.2 | 0.11 ± 0.03 | |
L-KYN/3-HK | 379.65 ± 286.47 | 444.32 ± 344.32 | |
TRP/3-HK | 31,612.86 ± 6224.3 | 30,379.05 ± 4953.80 | |
Cerebellum | TRP/L-KYN | 2.76 ± 0.27 | 3.02 ± 0.41 |
TRP/KYNA | 2447.12 ± 1695.8 | 2674.72 ± 1731.6 | |
L-KYN/KYNA | 878.78 ± 551.86 | 932.41 ± 684.18 | |
3-HK/KYNA | 2.94 ± 2.06 | 2.76 ± 1.88 | |
L-KYN/3-HK | 309.38 ± 50.33 | 337.17 ± 62.25 | |
TRP/3-HK | 846.61 ± 92.04 | 979.53 ± 241.18 |
Brain Structure | Ratio | Control | Memantine |
---|---|---|---|
Cortex | TRP/L-KYN | 22.75 ± 3.32 | 21.77 ± 5.32 |
TRP/KYNA | 884.59 ± 215.72 | 538.89 ± 133.31 *** | |
L-KYN/KYNA | 38.91 ± 7.81 | 25.26 ± 6.02 *** | |
3-HK/KYNA | 1.81 ± 7.81 | 1.31 ± 0.45 * | |
L-KYN/3-HK | 22.16 ± 4.18 | 25.97 ± 26.97 | |
TRP/3-HK | 505.73 ± 127.97 | 550.86 ± 571.44 | |
Striatum | TRP/L-KYN | 3.60 ± 1.2 | 3.95 ± 0.99 |
TRP/KYNA | 299.95 ± 408.26 | 181.32 ± 68.63 | |
L-KYN/KYNA | 93.86 ± 138.85 | 49.90 ± 24.95 | |
3-HK/KYNA | 22.16 ± 30.61 | 11.39 ± 5.33 | |
L-KYN/3-HK | 4.51 ± 1.94 | 4.44 ± 1.4 | |
TRP/3-HK | 15.31 ± 5.62 | 17.15 ± 5.64 | |
Hippocampus | TRP/L-KYN | 62.16 ± 16.1 | 63.61 ± 13.45 |
TRP/KYNA | 3802.30 ± 1049.0 | 3931.92 ± 574.18 | |
L-KYN/KYNA | 65.08 ± 26.44 | 65.13 ± 20.93 | |
3-HK/KYNA | 0.12 ± 0.04 | 0.12 ± 0.04 | |
L-KYN/3-HK | 543.07 ± 107.78 | 609.24 ± 32.34 | |
TRP/3-HK | 32,729.5 ± 7261.1 | 36,714.22 ± 17,194.0 | |
Cerebellum | TRP/L-KYN | 3.61 ± 0.36 | 3.95 ± 0.73 |
TRP/KYNA | 30,569.45 ± 2183.7 | 6036.42 ± 7106.3 | |
L-KYN/KYNA | 829.24 ± 550.91 | 1608.47 ± 1765.0 | |
3-HK/KYNA | 2.73 ± 1.68 | 4.90 ± 4.39 | |
L-KYN/3-HK | 309.89 ± 73.12 | 318.28 ± 84.6 | |
TRP/3-HK | 1111.99 ± 251.04 | 1260.31 ± 417.52 |
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Kloc, R.; Urbanska, E.M. Memantine and the Kynurenine Pathway in the Brain: Selective Targeting of Kynurenic Acid in the Rat Cerebral Cortex. Cells 2024, 13, 1424. https://doi.org/10.3390/cells13171424
Kloc R, Urbanska EM. Memantine and the Kynurenine Pathway in the Brain: Selective Targeting of Kynurenic Acid in the Rat Cerebral Cortex. Cells. 2024; 13(17):1424. https://doi.org/10.3390/cells13171424
Chicago/Turabian StyleKloc, Renata, and Ewa M. Urbanska. 2024. "Memantine and the Kynurenine Pathway in the Brain: Selective Targeting of Kynurenic Acid in the Rat Cerebral Cortex" Cells 13, no. 17: 1424. https://doi.org/10.3390/cells13171424
APA StyleKloc, R., & Urbanska, E. M. (2024). Memantine and the Kynurenine Pathway in the Brain: Selective Targeting of Kynurenic Acid in the Rat Cerebral Cortex. Cells, 13(17), 1424. https://doi.org/10.3390/cells13171424