Document Type
Article
Journal Title
Scientific Reports
Publication Date
2016
Volume
6
Abstract
Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15-16 weeks after LE using multi-array silicon probe electrodes implanted in the dorsal hippocampus, are reduced in PAF-r antagonist-treated mice. We suggest that over-activation of PAF-r signaling induces aberrant neuronal plasticity in LE and leads to chronic dysfunctional neuronal circuitry that mediates epilepsy.
MeSH Headings
Animals, Blood Platelets, Dendritic Spines, Disease Models, Animal, Epilepsy, Temporal Lobe, Hippocampus, Humans, Limbic Lobe, Mice, Neuronal Plasticity, Neurons, Platelet Activating Factor, Platelet Membrane Glycoproteins, Receptors, G-Protein-Coupled
DOI Link
ISSN
2045-2322
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Musto, Alberto E.; Rosencrans, Robert F.; Walker, Chelsey P.; Bhattacharjee, Surjyadipta; Raulji, Chittalsinh M.; Belayev, Ludmila; Fang, Zhide; Gordon, William C.; and Bazan, Nicolas G., "Dysfunctional Epileptic Neuronal Circuits and Dysmorphic Dendritic Spines are Mitigated by Platelet-Activating Factor Receptor Antagonism" (2016). Journal Articles: Pediatrics. 52.
https://digitalcommons.unmc.edu/com_peds_articles/52