RT Journal Article
T1 Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the ofspring of mice
A1 López Escobar, Beatriz
A1 Fernández Torres, Rut
A1 Ybot González, Patricia
AB The use of frst and second generation antiepileptic drugs during pregnancy doubles the risk of majorcongenital malformations and other teratogenic defects. Lacosamide (LCM) is a third-generationantiepileptic drug that interacts with collapsing response mediator protein 2, a protein that has beenassociated with neurodevelopmental diseases like schizophrenia. The aim of this study was to test thepotential teratogenic efects of LCM on developing embryos and its efects on behavioural/histologicalalterations in adult mice. We administered LCM to pregnant mice, assessing its presence, and thatof related compounds, in the mothers’ serum and in embryonic tissues using liquid chromatographycoupled to quadrupole/time of fight mass spectrometry detection. Embryo morphology wasevaluated, and immunohistochemistry was performed on adult ofspring. Behavioural studies werecarried out during the frst two postnatal weeks and on adult mice. We found a high incidence ofembryonic lethality and malformations in mice exposed to LCM during embryonic development.Neonatal mice born to dams treated with LCM during gestation displayed clear psychomotor delayand behavioural and morphological alterations in the prefrontal cortex, hippocampus and amygdalathat were associated with behaviours associated with schizophrenia spectrum disorders in adulthood.We conclude that LCM and its metabolites may have teratogenic efects on the developing embryos,refected in embryonic lethality and malformations, as well as behavioural and histological alterationsin adult mice that resemble those presented by patients with schizophrenia
PB Springer
SN 2045-2322 (electrónico)
YR 2020
FD 2020
LK https://hdl.handle.net/10272/23937
UL https://hdl.handle.net/10272/23937
LA eng
NO López-Escobar, B., Fernández-Torres, R., Vargas-López, V., Villar-Navarro, M., Rybkina, T., Rivas-Infante, E., Hernández-Viñas, A., Álvarez del Vayo, C., Caro-Vega, J., Sánchez-Alcázar, J. A., González-Meneses, A., Carrión, M. Á., & Ybot-González, P. (2020). Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice. In Scientific Reports (Vol. 10, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1038/s41598-020-64626-9
NO We are very thankful to Mark Sefton and Miguel Ruiz-Veguilla for revising the manuscript and valuablecomments on the manuscript. We also gratefully acknowledge Servicio de Microanalisis de la Universidad deSevilla (CITIUS) for the support ofered with UPLC-QTOF/MS. Tis work was supported by the AndalusianRegional Ministry of Economy, Science and Innovation (P11-cts-7634); the Andalusian Regional Ministryof Health (PI-0438-2010) and the Instituto de Salúd Carlos III (PS09/00050, CP08/00111, CPII14/00033) cofnanced by European Development Regional Fund “A way to achieve Europe” ERDF to PYG; Fundación RamónAreces, DGICYT BFU2011-27207, and the Junta de Andalucía CTS-2257 to AMC; Funding FEDER ProjectUNSE10–1E-429 to RFT and MVN; Francisco José de Caldas fellowship by COLCIENCIAS to V.V-L
DS Repositorio Institucional de la Universidad de Huelva
RD 31 may 2026