Acetylcholine receptor agonist effect on seizure activity and GABAergic mechanisms involved in prolonged febrile seizure development in an animal model.

In this study, α7-nAchRs were activated by using PNU-282,987 (PNU), a selective α7-nAchR agonist, in order to evaluate their effect in seizure threshold as well as GABAergic parameters in a PFS rat model. PFS was induced on 14-day old Sprague-Dawley rat pups by administration of lipopolysaccharide (217 ug/kg, i.p) followed 2.5 hours later by kainic acid (KA) (1.83 mg/kg, i.p). PNU was given prior to KA administration and Methyllycaconitine (MLA), an α7-nAchR antagonist, was given following KA injection. Seizure activity was recorded and monitored for one hour following seizure induction. Glutamate decarboxylase (GAD)1 and GAD 2 expression as well as GABA concentration in the hippocampus were assessed. Our results show that activating α7-nAchRs delays PFS progression and this delay was attenuated by the antagonist, MLA. Exposure to PFS reduced the expression of GAD1 and GABA concentration while PNU injection prevented this decrease. This suggests that specific nicotinic acetylcholine receptors may be used as therapeutic targets in the maintenance of adequate hippocampal GABA concentration for the prevention of PFS development. PMID: 31051225 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research