Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking
Abstract
1. Introduction
2. Results
2.1. Immunolocalization of CB1 Receptors in DG Neurons and Astrocytes
2.2. Expression and CB1 Receptor Coupling to Gαi/o Proteins in Hippocampal Synaptosomes
2.3. MPP Excitatory Synaptic Transmission and Plasticity
2.4. Learning and Memory in the Barnes Maze Test
3. Discussion
3.1. Omega-3 Supplementation During Abstinence Alters ECS and CB1 Receptor Signaling Molecules Following Adolescent Binge Drinking
3.2. Omega-3 Supplementation During Abstinence Mitigates Long-Lasting Cognitive Deficits Caused by Adolescent Binge Drinking
3.3. Experimental Limitations
4. Materials and Methods
4.1. Ethics Statement
4.2. Animal Treatment
4.3. Pre-Embedding Immunogold and Immunoperoxidase for Electron Microscopy
4.4. Synaptosomal Fractionation
4.5. Western Blot Analysis
4.6. [35S]GTPγS Binding Assays
4.7. Slice Preparation and Extracellular Field Recording
4.8. Barnes Maze Test
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Control | EtOH | n-3-EtOH | n-3-H2O | |
---|---|---|---|---|
CB1 receptor | 100.00 ± 6.58 | 138.16 ± 11.72 * | 152.86 ± 3.04 *** | 137.05 ± 14.28 * |
Crip1a | 100.00 ± 9.44 | 142.91 ± 13.27 * | 194.56 ± 19.08 *** | 149.96 ± 12.53 *** |
Gαo | 100.00 ± 1.75 | 92.88 ± 2.48 | 84.53 ± 4.98 | 67.22 ± 8.86 * |
Gαi1 | 100.00 ± 9.10 | 98.56 ± 6.81 | 91.00 ± 7.07 | 84.68 ± 5.59 |
Gαi2 | 100.00 ± 10.94 | 128.07 ± 15.63 | 91.78 ± 1.05 | 102.10 ± 6.52 |
Gαi3 | 100.00 ± 0.11 | 93.88 ± 5.60 | 97.63 ± 3.98 | 74.49 ± 10.65 |
Control | EtOH | n-3-EtOH | n-3-H2O | |
---|---|---|---|---|
PLCβ1 | 100.00 ± 5.52 | 108.81 ± 12.243 | 138.29 ± 9.55 ** | 129.69 ± 7.92 ** |
DAGLα | 100.00 ± 3.68 | 106.82 ± 3.43 | 20.42 ± 1.93 ***ϕϕ | 47.88 ± 10.29 ***ϕϕϕϯϯ |
DAGLβ | 100.00 ± 12.11 | 88.45 ± 16.12 | 147.39 ± 15.31 | 135.91 ± 16.12 |
MAGL | 100.00 ± 8.78 | 150.46 ± 14.23 * | 150.73± 15.47 * | 132.74 ± 7.41 * |
NAPE-PLD | 100.00 ± 6.60 | 118.94 ± 11.82 | 87.31 ± 11.61 | 108.81 ± 18.54 |
FAAH | 100.00 ± 9.50 | 113.29 ± 11.01 | 106.84 ± 13.41 | 99.02 ± 4.09 |
Standard Diet | N-3 Enriched Diet | |||
---|---|---|---|---|
Fats (%) | 4.0 | 5.9 | ||
mg/kg | % of total fats | mg/kg | % of total fats | |
SFA | 6000 | 15.0 | 11,867 | 20.1 |
PUFA | 21,000 | 52.5 | 31,129 | 52.8 |
Omega-3 | 1000 | 2.5 | 5437 | 9.2 |
Omega-6 | 20,000 | 50.0 | 25,679 | 43.5 |
Ratio omega-6/omega-3 | - | 20.0 | - | 4.7 |
EPA | 0 | 0 | 1325 | 2.2 |
DHA | 0 | 0 | 899 | 1.5 |
Drug | Action | Concentration (μM) |
---|---|---|
AM251 | CB1 antagonist | 4 |
AMG9810 | TRPV1 antagonist | 3 |
AM404 | AEA reuptake inhibitor | 30 |
URB597 | FAAH inhibitor | 2 |
LEI401 | NAPE-PLD inhibitor | 10 |
D-AP5 | NMDA antagonist | 50 |
Lat.A | Actin assembly inhibitor | 500 |
ω-conotoxin GVIA | N-type Ca2+ channels blockade | 1 |
THL | DGL inhibitor | 10 |
WIN-2 | CB1 agonist | 5 |
Capsaicin | TRPV1 agonist | 1 |
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Serrano, M.; Saumell-Esnaola, M.; Ocerin, G.; García del Caño, G.; Soria-Gómez, E.; Mimenza, A.; Puente, N.; Bonilla-Del Río, I.; Ramos-Uriarte, A.; Reguero, L.; et al. Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking. Int. J. Mol. Sci. 2025, 26, 5507. https://doi.org/10.3390/ijms26125507
Serrano M, Saumell-Esnaola M, Ocerin G, García del Caño G, Soria-Gómez E, Mimenza A, Puente N, Bonilla-Del Río I, Ramos-Uriarte A, Reguero L, et al. Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking. International Journal of Molecular Sciences. 2025; 26(12):5507. https://doi.org/10.3390/ijms26125507
Chicago/Turabian StyleSerrano, Maitane, Miquel Saumell-Esnaola, Garazi Ocerin, Gontzal García del Caño, Edgar Soria-Gómez, Amaia Mimenza, Nagore Puente, Itziar Bonilla-Del Río, Almudena Ramos-Uriarte, Leire Reguero, and et al. 2025. "Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking" International Journal of Molecular Sciences 26, no. 12: 5507. https://doi.org/10.3390/ijms26125507
APA StyleSerrano, M., Saumell-Esnaola, M., Ocerin, G., García del Caño, G., Soria-Gómez, E., Mimenza, A., Puente, N., Bonilla-Del Río, I., Ramos-Uriarte, A., Reguero, L., Christie, B. R., Rodríguez de Fonseca, F., Rodríguez-Arias, M., Gerrikagoitia, I., & Grandes, P. (2025). Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking. International Journal of Molecular Sciences, 26(12), 5507. https://doi.org/10.3390/ijms26125507