RT Journal Article
T1 Sex-specific alterations in emotional behavior and neurotransmitter systems in LPA1 receptor-deficient mice
A1 Sánchez-Marín, Laura
A1 Jiménez-Castilla, Violeta
A1 Flores-López, María
A1 Navarro Galera, Juan Antonio
A1 Gavito, Ana Luisa
A1 Blanco-Calvo, Eduardo
A1 Santín-Núñez, Luis Javier
A1 Pavón-Morón, Francisco Javier
A1 Rodriguez-de-Fonseca, Fernando
A1 Serrano, Antonia
K1 Dimorfismo sexual en animales
K1 Fosfolípidos
K1 Ratones de laboratorio - Hábitos y conducta
K1 Receptores de neurotransmisores
AB Lysophosphatidic acid (LPA) and the endocannabinoid system (ECS) are critical lipid signaling pathways involved in emotional regulation and behavior. Despite their interconnected roles and shared metabolic pathways, the specific contributions of LPA signaling through the LPA1 receptor to stress-related disorders remain poorly understood. This study investigates the effects of LPA1 receptor deficiency on emotional behavior and neurotransmitter-related gene expression, with a focus on sex-specific differences, using maLPA1-null mice of both sexes. We hypothesized LPA1 receptor loss disrupts the interplay between LPA and the endocannabinoid 2-arachidonoylglycerol (2-AG) signaling, resulting in distinct behavioral and molecular alterations. maLPA1-null mice exhibited increased anxiety-like behaviors and altered stress-coping responses compared to wild-type counterparts, with more pronounced effects observed in females. Female mice also displayed higher corticosterone levels, though no genotype-related differences were observed. Plasma analyses revealed elevated LPA levels in maLPA1-null mice, suggesting a compensatory mechanism, and reduced 2-AG levels, indicating impaired ECS signaling. Gene expression profiling in the amygdala and medial prefrontal cortex showed significant alterations in the gene expression of key components of LPA and 2-AG signaling pathways, as well as neuropeptide systems such as corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY). Glutamatergic signaling components also exhibited sex-specific variations. These findings suggest that LPA1 receptor deficiency impacts behavioral response and disrupts sex-specific neurotransmitter signaling, emphasizing the importance of LPA-ECS crosstalk in emotional regulation. This study provides insights into the molecular mechanisms underlying stress-related disorders such as depression and anxiety, which may inform the development of sex-specific therapeutic approaches.
PB Elsevier
SN 0028-3908
YR 2025
FD 2025-01-24
LK https://hdl.handle.net/10630/38542
UL https://hdl.handle.net/10630/38542
LA eng
NO Sánchez-Marín, L., Jiménez-Castilla, V., Flores-López, M., Navarro, J. A., Gavito, A., Blanco-Calvo, E., Santín, L. J., Pavón-Morón, F. J., Rodríguez de Fonseca, F., & Serrano, A. (2025). Sex-specific alterations in emotional behavior and neurotransmitter systems in LPA1 receptor-deficient mice. Neuropharmacology, 268, 110325.
NO Funding for open access charge: Universidad de Málaga / CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 25 ene 2026