RT Journal Article
T1 Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice
A1 López-Escobar, Beatriz
A1 Fernández-Torres, Rut
A1 Vargas-López, Viviana
A1 Villar-Navarro, Mercedes
A1 Rybkina, Tatyana
A1 Rivas-Infante, Eloy
A1 Hernández-Viñas, Ayleen
A1 Álvarez Del Vayo, Concepción
A1 Caro-Vega, José
A1 Sánchez-Alcázar, José A.
A1 González-Meneses, Antonio
A1 Carrión, M. Ángel
A1 Ybot-González, Patricia
K1 Lacosamide
K1 Animales
K1 Mice
K1 Fetus
K1 Dose-response relationship, drug
K1 Memory
K1 Pregnancy
K1 Schizophrenia
K1 Malformations
K1 Lacosamida
K1 Animales
K1 Ratones
K1 Feto
K1 Relación dosis-respuesta a droga
K1 Memoria
K1 Embarazo
K1 Esquizofrenia
K1 Anomalías congénitas
K1 Efectos tardíos de la exposición prenatal
AB The use of first and second generation antiepileptic drugs during pregnancy doubles the risk of major congenital malformations and other teratogenic defects. Lacosamide (LCM) is a third-generation antiepileptic drug that interacts with collapsing response mediator protein 2, a protein that has been associated with neurodevelopmental diseases like schizophrenia. The aim of this study was to test the potential teratogenic effects of LCM on developing embryos and its effects on behavioural/histological alterations in adult mice. We administered LCM to pregnant mice, assessing its presence, and that of related compounds, in the mothers' serum and in embryonic tissues using liquid chromatography coupled to quadrupole/time of flight mass spectrometry detection. Embryo morphology was evaluated, and immunohistochemistry was performed on adult offspring. Behavioural studies were carried out during the first two postnatal weeks and on adult mice. We found a high incidence of embryonic lethality and malformations in mice exposed to LCM during embryonic development. Neonatal mice born to dams treated with LCM during gestation displayed clear psychomotor delay and behavioural and morphological alterations in the prefrontal cortex, hippocampus and amygdala that were associated with behaviours associated with schizophrenia spectrum disorders in adulthood. We conclude that LCM and its metabolites may have teratogenic effects on the developing embryos, reflected in embryonic lethality and malformations, as well as behavioural and histological alterations in adult mice that resemble those presented by patients with schizophrenia.
PB Springer Nature
YR 2020
FD 2020-05-06
LK http://hdl.handle.net/10668/3717
UL http://hdl.handle.net/10668/3717
LA en
NO López-Escobar B, Fernández-Torres R, Vargas-López V, Villar-Navarro M, Rybkina T, Rivas-Infante E, et al. Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice. Sci Rep. 2020 May 6;10(1):7615
DS RISalud
RD Apr 6, 2025