Abstract
Epilepsy is one of the most common neurological disorders – estimated to affect at least 65 million worldwide. Most of the epilepsy research has so far focused on how to dampen neuronal discharges and to explain how changes in intrinsic neuronal activity or network function cause seizures. As a result, pharmacological therapy has largely been limited to symptomatic treatment targeted at neurons. Given the expanding spectrum of functions ascribed to the non-neuronal constituents of the brain, in both physiological brain function and in brain disorders, it is natural to closely consider the roles of astrocytes in epilepsy. It is now widely accepted that astrocytes are key controllers of the composition of the extracellular fluids, and may directly interact with neurons by releasing gliotransmitters. A central tenet is that astrocytic intracellular Ca2+ signals promote release of such signaling substances, either through synaptic or non-synaptic mechanisms. Accruing evidence suggests that astrocytic Ca2+ signals play important roles in both seizures and epilepsy, and this review aims to highlight the current knowledge of the roles of this central astrocytic signaling mechanism in ictogenesis and epileptogenesis.
Highlights
Epilepsy is one of the most common neurological disorders – estimated to affect around 1% of the world’s population (Hesdorffer et al, 2011; Neligan et al, 2012; Beghi, 2016)
While astrocytes in the adult brain are almost depleted of mGluR5 (Sun et al, 2013), the receptor is consistently expressed in chronic epilepsy models and resected tissue from patients with epilepsy (Aronica et al, 2000, 2003), and a recent study has shown that mGluR5 expression and mGluR5-dependent Ca2+ transients reemerge during epileptogenesis along with an increase in glutamate uptake (Umpierre et al, 2019)
It is possible that prolonged epileptic activity and increased Ca2+ signaling in astrocytic endfeet, as we demonstrated in Szokol et al (2015), activate Ca2+ dependent proteases like calpain (Nagelhus and Ottersen, 2013), that shows affinity to dystrophin and could cleave the dystrophin associated protein complex (DAPC) (Figure 1; Shields et al, 2000)
Summary
Epilepsy is one of the most common neurological disorders – estimated to affect around 1% of the world’s population (Hesdorffer et al, 2011; Neligan et al, 2012; Beghi, 2016). Later, Ding et al (2007) were able to demonstrate increased astrocytic Ca2+ signaling in an in vivo pilocarpine epilepsy model.
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