Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

Abstract

BackgroundEpidemiological 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.MethodsPregnant 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).ResultsTwo 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.DiscussionPrenatal 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.

Simultaneous Cardiac and Neurological Monitoring to Assess Chemical Exposures and Drug Toxicity in Xenopus Laevis

“…After recalculation, the ictal events in the VPA+PTZ group in the 1500-second-long recording appeared 9 times, resulting in a 73.5% reduction in comparison with the PTZ group subject. These results proved that VPA can mitigate PTZinduced seizures in terms of occurrences and intensities which is in accordance with studies on other models (Puig-Lagunes et al 2016;Romoli et al 2019). The recordings obtained from different groups also validate our device for its capability and longevity to collect high SNR EEG for long term monitoring.…”

Downregulation of the GABAA receptor β2 subunit in a rat model of autism

“…Reduced expression of GARB2, which indirectly indicates reduced availability of GABAA receptors, may contribute to social deficits 25,38,39 and other neurological changes observed in the VPA rat model, such as increased seizure susceptibility. 25,30 The gene encoding GARB2 has been previously associated with a higher risk of ASD. did not identified differences in the levels of GABAA receptors or their α5 subunit in the frontal cortex, cingulate cortex, caudate/putamen, dorsal hippocampus, cerebellum, or amygdala between these three models or compared to control mice.…”

“…Females were housed individually and allowed to rear their litters. 30 Experiments to assess GARB2 immunoreactivity were performed on postnatal day 14 (P14) rat pups. The SS group consisted of 9 rats (3 males and 6 females), while the VPA group consisted of 10 rats (8 males and 2 females).…”

The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities

“…The authors speculate that the seizure protective effect of prenatal VPA may be due to an increase in fetal levels of GABA and changes in drug metabolism promoting an increased degradation of PTZ. The reason for being highly susceptible to PTZ was thought to be an under-development of the GABAergic system ( Puig-Lagunes et al, 2016 ).…”