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Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking Serrano, Maitane; Saumell-Esnaola, Miquel; Ocerin, Garazi; García del Caño, Gontzal; Soria-Gómez, Edgar; Mimenza, Amaia; Puente, Nagore; Bonilla-Del Río, Itziar; Ramos-Uriarte, Almudena; Reguero, Leire; Christie, Brian R.; Rodríguez de Fonseca, Fernando; Rodríguez-Arias, Marta; Gerrikagoitia, Inmaculada; Grandes, Pedro

Abstract

Adolescent binge drinking has lasting behavioral consequences by disrupting the endocannabinoid system (ECS) and depleting brain omega-3. The natural accumulation of omega-3 fatty acids in cell membranes is crucial for maintaining the membrane structure, supporting interactions with the ECS, and restoring synaptic plasticity and cognition impaired by prenatal ethanol (EtOH) exposure. However, it remains unclear whether omega-3 supplementation can mitigate the long-term effects on the ECS, endocannabinoid-dependent synaptic plasticity, and cognition following adolescent binge drinking. Here, we demonstrated that omega-3 supplementation during EtOH withdrawal increases CB1 receptors in hippocampal presynaptic terminals of male mice, along with the recovery of receptor-stimulated [35S]GTPγS binding to Gαi/o proteins. These changes are associated with long-term potentiation (LTP) at excitatory medial perforant path (MPP) synapses in the dentate gyrus (DG), which depends on anandamide (AEA), transient receptor potential vanilloid 1 (TRPV1), and N-methyl-D-aspartate (NMDA) receptors. Finally, omega-3 intake following binge drinking reduced the time and number of errors required to locate the escape box in the Barnes maze test. Collectively, these findings suggest that omega-3 supplementation restores Barnes maze performance to levels comparable to those of control mice after adolescent binge drinking. This recovery is likely mediated by modulation of the hippocampal ECS, enhancing endocannabinoid-dependent excitatory synaptic plasticity.

Item Metadata

Title
Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking
Creator
Serrano, Maitane; Saumell-Esnaola, Miquel; Ocerin, Garazi; García del Caño, Gontzal; Soria-Gómez, Edgar; Mimenza, Amaia; Puente, Nagore; Bonilla-Del Río, Itziar; Ramos-Uriarte, Almudena; Reguero, Leire; Christie, Brian R.; Rodríguez de Fonseca, Fernando; Rodríguez-Arias, Marta; Gerrikagoitia, Inmaculada; Grandes, Pedro
Contributor
Djavad Mowafaghian Centre for Brain Health; Island Medical Program
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2025-06-09
Description
Adolescent binge drinking has lasting behavioral consequences by disrupting the endocannabinoid system (ECS) and depleting brain omega-3. The natural accumulation of omega-3 fatty acids in cell membranes is crucial for maintaining the membrane structure, supporting interactions with the ECS, and restoring synaptic plasticity and cognition impaired by prenatal ethanol (EtOH) exposure. However, it remains unclear whether omega-3 supplementation can mitigate the long-term effects on the ECS, endocannabinoid-dependent synaptic plasticity, and cognition following adolescent binge drinking. Here, we demonstrated that omega-3 supplementation during EtOH withdrawal increases CB1 receptors in hippocampal presynaptic terminals of male mice, along with the recovery of receptor-stimulated [35S]GTPγS binding to Gαi/o proteins. These changes are associated with long-term potentiation (LTP) at excitatory medial perforant path (MPP) synapses in the dentate gyrus (DG), which depends on anandamide (AEA), transient receptor potential vanilloid 1 (TRPV1), and N-methyl-D-aspartate (NMDA) receptors. Finally, omega-3 intake following binge drinking reduced the time and number of errors required to locate the escape box in the Barnes maze test. Collectively, these findings suggest that omega-3 supplementation restores Barnes maze performance to levels comparable to those of control mice after adolescent binge drinking. This recovery is likely mediated by modulation of the hippocampal ECS, enhancing endocannabinoid-dependent excitatory synaptic plasticity.
Subject
alcohol; CB1 receptor; hippocampus; memory; polyunsaturated fatty acids; synaptic plasticity
Genre
Article
Type
Text
Language
eng
Date Available
2025-07-04
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0449266
URI
http://hdl.handle.net/2429/91504
Affiliation
Medicine, Faculty of; Non UBC; Cellular and Physiological Sciences, Department of
Citation
International Journal of Molecular Sciences 26 (12): 5507 (2025)
Publisher DOI
10.3390/ijms26125507
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher; Other
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0