Upregulation of GLT-1 Expression Attenuates Neuronal Apoptosis and Cognitive Dysfunction via Inhibiting the CB1-CREB Signaling Pathway in Mice with Traumatic Brain Injury
Abstract
1. Background
2. Materials and Methods
2.1. Animals
2.2. Controlled Cortical Impact (CCI) Model
2.3. Behavior Test
2.3.1. Open Field Test
2.3.2. Novel Object Recognition Test
2.3.3. Y-Maze Test
2.4. Drug Administration
2.5. Brain Tissue Harvest and Protein Level Quantification
2.6. Western Blot
2.7. Immunofluorescence
2.8. TUNEL Staining
2.9. Statistical Analysis
3. Results
3.1. The Downregulation of GLT-1 Expression in Astrocytes Resulting from TBI Was Effectively Reversed by Inhibiting the CB1 Receptor
3.2. Reversing the Decrease in GLT-1 Expression Reduced Neuronal Apoptosis in the CA3 and DG Subregions of Mice with TBI
3.3. GLT-1 Expression in the Hippocampus Was Significantly Increased by Inhibiting the CB1-CREB Signaling Pathway
3.4. The Cognitive Impairment Resulting from TBI Was Improved by Inhibiting the CB1 Receptor
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
| 2-AG | 2-arachidonoyl glycerol |
| CB1 | Cannabinoid type 1 |
| CCI | Controlled cortical impact |
| CREB | Cyclic-AMP response binding protein |
| DMEM | Dulbecco’s modified Eagle’s medium |
| EAATs | Excitatory amino acid transporters |
| ECS | Endocannabinoid system |
| ERK | Extracellular signal-regulated kinase |
| FBS | Fetal bovine serum |
| GFAP | Glial fibrillary acidic protein |
| GLAST | Glutamate and aspartate transporter |
| GLT-1 | Glutamate transporter-1 |
| IF | Immunofluorescence |
| MAGL | Monoacyl glycerol lipase |
| mTOR | Mammalian target of rapamycin |
| NF-κB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
| PKA | Protein kinase A |
| RI | Recognition Index |
| TBI | Traumatic brain injury |
| WB | Western blot |
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Bu, B.; Ma, R.; Wang, C.; Jiang, S.; Xu, X. Upregulation of GLT-1 Expression Attenuates Neuronal Apoptosis and Cognitive Dysfunction via Inhibiting the CB1-CREB Signaling Pathway in Mice with Traumatic Brain Injury. Biomolecules 2025, 15, 1408. https://doi.org/10.3390/biom15101408
Bu B, Ma R, Wang C, Jiang S, Xu X. Upregulation of GLT-1 Expression Attenuates Neuronal Apoptosis and Cognitive Dysfunction via Inhibiting the CB1-CREB Signaling Pathway in Mice with Traumatic Brain Injury. Biomolecules. 2025; 15(10):1408. https://doi.org/10.3390/biom15101408
Chicago/Turabian StyleBu, Bin, Ruiyao Ma, Chengyu Wang, Shukun Jiang, and Xiaoming Xu. 2025. "Upregulation of GLT-1 Expression Attenuates Neuronal Apoptosis and Cognitive Dysfunction via Inhibiting the CB1-CREB Signaling Pathway in Mice with Traumatic Brain Injury" Biomolecules 15, no. 10: 1408. https://doi.org/10.3390/biom15101408
APA StyleBu, B., Ma, R., Wang, C., Jiang, S., & Xu, X. (2025). Upregulation of GLT-1 Expression Attenuates Neuronal Apoptosis and Cognitive Dysfunction via Inhibiting the CB1-CREB Signaling Pathway in Mice with Traumatic Brain Injury. Biomolecules, 15(10), 1408. https://doi.org/10.3390/biom15101408
