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oai:riuma.uma.es:10630/453322026-04-10T09:02:00Zcom_10630_2254col_10630_37953
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Repositorio Institucional de la Universidad de Málaga author Medina-Vera, Dina author García-Bao, Alba author Medrano, Mireia author Martín-Chaves, Laura author Rodríguez-Capitán, Jorge author Rodríguez de Fonseca, Fernando author Serrano, Antonia author Jiménez-Navarro, Manuel Francisco author Valverde, Olga author Pavón-Morón, Francisco Javier 2026-02-10T11:29:45Z 2026 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 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. eng Attribution 4.0 International Síndrome alcohólico fetal Corazón - Enfermedades Riesgos para la salud Prenatal-lactational alcohol exposure induces sex-specific CX3CL1/CX3CR1 dysregulation linked to neuroendocrine imbalance and cardiovascular risk journal article 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 URL https://riuma.uma.es/bitstreams/34df920e-d8b6-4240-832c-86eacd6b54b2/download File MD5 cc48489db7f7fd5211f6998d6965c1fe 8720802 application/pdf 1-s2.0-S0889159126002114-main.pdf