La activación del sistema inmunológico materno como respuesta a una infección durante la gestación aumenta el riesgo de trastornos del neurodesarrollo. En este estudio hemos descubierto que la activación inmunitaria materna induce una alteración en la síntesis y modificación de proteínas clave para el desarrollo neuronal, especialmente MAP2, una proteína crucial para la estabilidad del citoesqueleto neuronal y el establecimiento de sinapsis.
Resumen
Alterations induced by maternal immune activation (MIA) during gestation impact the subsequent neurodevelopment of progeny, a process that in humans, has been linked to the development of several neuropsychiatric conditions. To undertake a comprehensive examination of the molecular mechanisms governing MIA, we have devised an in vitro model based on neural stem cells (NSCs) sourced from fetuses carried by animals subjected to Poly I:C treatment. These neural progenitors demonstrate proliferative capacity and can be effectively differentiated into both neurons and glial cells. Transcriptomic, proteomic, and phosphoproteomic analyses conducted on these cellular models, in conjunction with counterparts from control treatments, revealed discernible shifts in the expression levels of a specific subset of proteins implicated in neuronal function. Furthermore, the phosphoproteomic data highlighted a discernible discrepancy in the basal phosphorylation of proteins between differentiated cells from both experimental groups, particularly within proteins associated with cytoskeletal architecture and synaptic functionality, notably those belonging to the MAP family. Observed alterations in MAP phosphorylation were found to potentially have functional consequences as they correlate with changes in neuronal plasticity and the establishment of neuronal synapses. Our data agrees with previous published observations and further underscore the importance of MAP2 phosphorylation state on its function and the impact that this protein has in neuronal structure and function.
septiembre 2025
Sobre el grupo investigador
Este trabajo ha sido liderado por el grupo del Dr. Juan F. López-Giménez (CSIC), centrado en el estudio de los mecanismos moleculares implicados en la señalización de la serotonina. En el estudio también ha participado el grupo del Dr. Pedro R. Cutillas (Queen Mary University of London), especialista en proteómica y señalización celular. Asimismo, ha contado con la colaboración del Dr. Javier González-Maeso (Virginia Commonwealth University, EE.UU.), referente en neurofarmacología. El equipo ha combinado enfoques moleculares y proteómicos de vanguardia. Los resultados aportan nuevas claves para comprender la relación entre inmunidad materna y vulnerabilidad a trastornos psiquiátricos.
Referencia del artículo
Martín-Guerrero, S.M., Martín-Estebané, M., Lara Ordóñez, A.J. et al. Maternal immune activation imprints translational dysregulation and differential MAP2 phosphorylation in descendant neural stem cells. Mol Psychiatry 30, 2994–3007 (2025)
https://doi.org/10.1038/s41380-025-02905-5
