2026-05-27T12:54:51Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/453322026-04-10T09:02:00Zcom_10630_2254col_10630_37953

Prenatal-lactational alcohol exposure induces sex-specific CX3CL1/CX3CR1 dysregulation linked to neuroendocrine imbalance and cardiovascular risk Medina-Vera, Dina García-Bao, Alba Medrano, Mireia Martín-Chaves, Laura Rodríguez-Capitán, Jorge Rodríguez de Fonseca, Fernando Serrano, Antonia Jiménez-Navarro, Manuel Francisco Valverde, Olga Pavón-Morón, Francisco Javier Síndrome alcohólico fetal Corazón - Enfermedades Riesgos para la salud Fetal alcohol spectrum disorder is associated with lasting neurodevelopmental and cardiovascular dysfunctions. The fractalkine axis CX3CL1/CX3CR1, a chemokine and its sole known receptor expressed in microglia and myeloid/endothelial cells, coordinates neuroimmune and vascular responses. We tested whether prenatal-lactational alcohol exposure (PLAE) is associated with sex-specific dysregulation of this axis along with integrated behavioral, neuroendocrine, inflammatory, and cardiovascular signatures. Pregnant C57BL/6 dams consumed 20% ethanol using a drinking-in-the-dark (DID) paradigm throughout gestation and lactation. Adult offspring (PND60–70) underwent behavioral testing (elevated plus maze and tail suspension test); plasma profiling of corticosterone, cytokines/chemokines, endothelial/coagulation markers, and matrix-remodeling enzymes; and cardiac transcriptional assays for stress- and inflammation-related genes (including Cx3cr1). Analyses were stratified by sex. PLAE females exhibited increased anxiety-like behavior, two-fold higher plasma CX3CL1, and upregulated cardiac Cx3cr1 compared with control females. PLAE males showed no behavioral or endocrine changes but evidence of matrix remodeling (elevated proMMP-9, reduced sP-Selectin). Across sexes, PLAE was associated with a proinflammatory/endothelial-activation profile (elevated IL13, IL18, and PAI-1, reduced CXCL16, higher proMMP-9) and altered cardiac expression of Nr3c2, Tnfrsf1a, Tlr4, and Nfkbia, compatible with early vascular risk. Independent of exposure, females exhibited reduced immobility and higher corticosterone, IL5, IL13, sE-Selectin, and thrombomodulin. Plasma CX3CL1 correlated inversely with exploratory and stress-coping behaviors, and positively with corticosterone, inflammatory/vascular markers, and cardiac Cx3cr1 and Tnfrsf1a. PLAE is associated with sex-specific dysregulation of the CX3CL1/CX3CR1 axis and convergent neuroimmune-vascular signatures indicative of subclinical endothelial dysfunction. These associative findings support the hypothesis that fractalkine-pathway modulation may mitigate long-term neurobehavioral and cardiovascular vulnerability after PLAE, warranting causal testing. 2026 journal article Dina Medina-Vera, Alba García-Baos, Mireia Medrano, Laura Martín-Chaves, Jorge Rodríguez-Capitán, Fernando Rodríguez de Fonseca, Antonia Serrano, Manuel Jiménez-Navarro, Olga Valverde, Francisco Javier Pavón-Morón, Prenatal-lactational alcohol exposure induces sex-specific CX3CL1/CX3CR1 dysregulation linked to neuroendocrine imbalance and cardiovascular risk, Brain, Behavior, and Immunity, Volume 134, 2026, 106463, ISSN 0889-1591, https://doi.org/10.1016/j.bbi.2026.106463. https://hdl.handle.net/10630/45332 https://doi.org/10.1016/j.bbi.2026.106463 eng info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PI22%2F00427/ES/PAPEL DEL BDNF Y LAS ACILETANOLAMIDAS EN EL DETERIORO COGNITIVO ASOCIADO A LOS TRASTORNOS POR USO DE ALCOHOL: UN ESTUDIO TRASLACIONAL/ info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PI22%2F01833/ES/Caracterización de Marcadores de Estrés Cardíaco y Quimioquinas en Pacientes con Trastorno por Uso de Alcohol para Evaluar el Riesgo de Cardiopatía Isquémica: Biomarcadores Específicos/ http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International Elsevier