Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid
Background Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20–25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model....
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PeerJ Inc.
2016-11-01
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author | Angel A. Puig-Lagunes Jorge Manzo Luis Beltrán-Parrazal Consuelo Morgado-Valle Rebeca Toledo-Cárdenas Maria-Leonor López-Meraz |
author_facet | Angel A. Puig-Lagunes Jorge Manzo Luis Beltrán-Parrazal Consuelo Morgado-Valle Rebeca Toledo-Cárdenas Maria-Leonor López-Meraz |
author_sort | Angel A. Puig-Lagunes |
collection | DOAJ |
description | Background Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20–25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model. Methods Pregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo). Results Two subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA−) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals. Discussion Prenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy. |
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spelling | doaj.art-320fcefb9f3e46ecba13d703497423982023-12-02T21:54:23ZengPeerJ Inc.PeerJ2167-83592016-11-014e270910.7717/peerj.2709Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acidAngel A. Puig-Lagunes0Jorge Manzo1Luis Beltrán-Parrazal2Consuelo Morgado-Valle3Rebeca Toledo-Cárdenas4Maria-Leonor López-Meraz5Doctorado en Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, MexicoCentro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, MexicoCentro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, MexicoCentro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, MexicoCentro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, MexicoCentro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, MexicoBackground Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20–25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model. Methods Pregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo). Results Two subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA−) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals. Discussion Prenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.https://peerj.com/articles/2709.pdfEpilepsyConvulsionsAutismValproic acidPentylenetetrazole |
spellingShingle | Angel A. Puig-Lagunes Jorge Manzo Luis Beltrán-Parrazal Consuelo Morgado-Valle Rebeca Toledo-Cárdenas Maria-Leonor López-Meraz Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid PeerJ Epilepsy Convulsions Autism Valproic acid Pentylenetetrazole |
title | Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid |
title_full | Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid |
title_fullStr | Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid |
title_full_unstemmed | Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid |
title_short | Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid |
title_sort | pentylenetetrazole induced seizures in developing rats prenatally exposed to valproic acid |
topic | Epilepsy Convulsions Autism Valproic acid Pentylenetetrazole |
url | https://peerj.com/articles/2709.pdf |
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