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Schlagwörter:
Seizure, Hyperexcitable network, Ictogenesis, CB1, TRPV1, Endovanilloid, Neurogenesis, GABA, Glutamate, Amygdala
Zusammenfassung:
The endocannabinoid system serves as a retrograde negative feedback
mechanism. It is thought to control neuronal activity in an epileptic
neuronal network. The purpose of this study was to evaluate the impact
of the endocannabinoid and endovanilloid systems on both epileptogenesis
and ictogenesis.
Therefore, we modulated the endocannabinoid and endovanilloid systems
genetically and pharmacologically, and analyzed the subsequent impact on
seizure progression in the kindling model of temporal lobe epilepsy in
mice. In addition, the impact of seizures on associated cellular
alterations was evaluated.
Our principal results revealed that the endocannabinoid system affects
seizure and afterdischarge duration dependent on the neuronal
subpopulation being modulated. Genetic deletion of CBI-receptors (CB1Rs)
from principal neurons of the forebrain and pharmacological antagonism
with rimonabant (5 mg/kg) caused longer seizure duration. Deletion of
CB1R from GABAergic forebrain neurons resulted in the opposite effect.
Along with these findings, the CB1R density was elevated in animals with
repetitively induced seizures. However, neither genetic nor
pharmacological interventions had any impact on the development of
generalized seizures. Other than CBI, genetic deletion or
pharmacological blockade with SB366791 (1 mg/kg) of transient receptor
potential vanilloid receptor 1 (TRPV1) had no effect on the duration of
behavioral or electrographic seizure activity in the kindling model.
In conclusion, we demonstrate that endocannabinoid, but not
endovanilloid, signaling affects termination of seizure activity,
without influencing seizure severity over time. These effects are
dependent on the neuronal subpopulation. Thus, the data argue that the
endocannabinoid system plays an active role in seizure termination but
does not regulate epileptogenesis. (C) 2015 Elsevier Inc. All rights
reserved.
