Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice
| Autor: | José Manuel Caro-Vega, Beatriz López-Escobar, Antonio González-Meneses, Patricia Ybot-Gonzalez, Eloy Rivas-Infante, M. Ángel Carrión, Tatyana Rybkina, Mercedes Villar-Navarro, Rut Fernández-Torres, Ayleen Hernández-Viñas, Viviana Vargas-López, José Antonio Sánchez-Alcázar, Concepcion Álvarez del Vayo |
|---|---|
| Přispěvatelé: | Universidad de Sevilla. Departamento de Química Analítica, Instituto de Salud Carlos III, Junta de Andalucía, Fundación Ramón Areces, European Commission, Colciencias (Colombia), [López-Escobar,B, Hernández-Viñas,A, Caro-Vega,J, Ybot-González,P] Grupo de Neurodesarrollo, Hospital Universitario Virgen del Rocio/Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Sevilla, Spain. [Fernández-Torres,P, Villar-Navarro,M] Departamento de Química Analítica, Facultad Química, Universidad Sevilla, Sevilla, Spain. [Fernández-Torres,P] Centro de Investigación en Salud y Medio Ambiente (CYSMA), Universidad de Huelva, Huelva, Spain. [Vargas-López,V, Rybkina,V, Carrión,MA] Departamento de Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide, Sevilla, Spain. [Vargas-López,V] Behavioral Neurophysiology Laboratory, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia. [Rivas-Infante,E] Unidad de Gestión Clínica de Anatomía Patología, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Álvarez Del Vayo,C] Unidad de Gestión Clínica de Farmacia, Hospital Universitario Virgen del Rocío and Universidad de Sevilla, Sevilla, Spain. [Sánchez-Alcázar,JA] Centro Andaluz de Biología del Desarrollo (CABD), and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, CSIC, Universidad Pablo de Olavide, Sevilla, Spain. [González-Meneses,A] Unidad de Gestión Clínica de Pediatría, Hospital Universitario Virgen del Rocío and Universidad de Sevilla, Sevilla, Spain. [Ybot-González,P] Unidad de Gestión Clínica de Neurología y Neurofisiología, Hospital Universitario Virgen Macarena, Sevilla, Spain., This work was supported by the Andalusian Regional Ministry of Economy, Science and Innovation (P11-cts-7634), the Andalusian Regional Ministry of Health (PI-0438-2010) and the Instituto de Salúd Carlos III (PS09/00050, CP08/00111, CPII14/00033) co-financed by European Development Regional Fund 'A way to achieve Europe' ERDF to PYG, Fundación Ramón Areces, DGICYT BFU2011-27207, and the Junta de Andalucía CTS-2257 to AMC, Funding FEDER Project UNSE10–1E-429 to RFT and MVN, Francisco José de Caldas fellowship by COLCIENCIAS to V.V-L. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lacosamide Ratones Efectos tardíos de la exposición prenatal lcsh:Medicine Hippocampus Physiology Esquizofrenia Feto Mice 0302 clinical medicine Pregnancy Lacosamida Organisms::Eukaryota::Animals [Medical Subject Headings] Anomalías congénitas lcsh:Science Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings] Multidisciplinary Incidence Embryo Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Prenatal Injuries::Prenatal Exposure Delayed Effects [Medical Subject Headings] Relación dosis-respuesta a droga Schizophrenia Prenatal Exposure Delayed Effects Malformations Gestation Female Anatomy::Embryonic Structures::Fetus [Medical Subject Headings] Locomotion medicine.drug Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Memory [Medical Subject Headings] Embarazo Offspring Article 03 medical and health sciences Fetus Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings] Memory Developmental biology Psychiatry and Psychology::Mental Disorders::Schizophrenia and Disorders with Psychotic Features::Schizophrenia [Medical Subject Headings] Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Anticonvulsants [Medical Subject Headings] medicine Memoria Animals Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] Dose-Response Relationship Drug business.industry Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Dose-Response Relationship Drug [Medical Subject Headings] lcsh:R Embryogenesis medicine.disease Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Locomotion [Medical Subject Headings] Affect 030104 developmental biology Check Tags::Female [Medical Subject Headings] Animales lcsh:Q business 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | Scientific Reports Digital.CSIC. Repositorio Institucional del CSIC instname idUS: Depósito de Investigación de la Universidad de Sevilla Universidad de Sevilla (US) Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) idUS. Depósito de Investigación de la Universidad de Sevilla |
| Popis: | 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. This work was supported by the Andalusian Regional Ministry of Economy, Science and Innovation (P11-cts-7634); the Andalusian Regional Ministry of Health (PI-0438-2010) and the Instituto de Salúd Carlos III (PS09/00050, CP08/00111, CPII14/00033) co-financed by European Development Regional Fund “A way to achieve Europe” ERDF to PYG; Fundación Ramón Areces, DGICYT BFU2011-27207, and the Junta de Andalucía CTS-2257 to AMC; Funding FEDER Project UNSE10–1E-429 to RFT and MVN; Francisco José de Caldas fellowship by COLCIENCIAS to V.V-L. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|