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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Main Authors: Angel A. Puig-Lagunes, Jorge Manzo, Luis Beltrán-Parrazal, Consuelo Morgado-Valle, Rebeca Toledo-Cárdenas, Maria-Leonor López-Meraz
Format: Article
Language:English
Published: PeerJ Inc. 2016-11-01
Series:PeerJ
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Online Access:https://peerj.com/articles/2709.pdf
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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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