RT Journal Article
T1 Prenatal-lactational alcohol exposure induces sex-specific CX3CL1/CX3CR1 dysregulation linked to neuroendocrine imbalance and cardiovascular risk
A1 Medina-Vera, Dina
A1 García-Bao, Alba
A1 Medrano, Mireia
A1 Martín-Chaves, Laura
A1 Rodríguez-Capitán, Jorge
A1 Rodríguez de Fonseca, Fernando
A1 Serrano, Antonia
A1 Jiménez-Navarro, Manuel Francisco
A1 Valverde, Olga
A1 Pavón-Morón, Francisco Javier
K1 Síndrome alcohólico fetal
K1 Corazón - Enfermedades
K1 Riesgos para la salud
AB 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.
PB Elsevier
YR 2026
FD 2026
LK https://hdl.handle.net/10630/45332
UL https://hdl.handle.net/10630/45332
LA eng
NO 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.
NO Funding for open access charge: Universidad de Málaga / CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 28 feb 2026