Royal College of Surgeons in Ireland
Astrocyte-neuron circuits in epilepsy.pdf (2.61 MB)

Astrocyte-neuron circuits in epilepsy

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journal contribution
posted on 2023-03-22, 17:32 authored by Benton S Purnell, Mariana AlvesMariana Alves, Detlev Boison

The epilepsies are a diverse spectrum of disease states characterized by spontaneous seizures and associated comorbidities. Neuron-focused perspectives have yielded an array of widely used anti-seizure medications and are able to explain some, but not all, of the imbalance of excitation and inhibition which manifests itself as spontaneous seizures. Furthermore, the rate of pharmacoresistant epilepsy remains high despite the regular approval of novel anti-seizure medications. Gaining a more complete understanding of the processes that turn a healthy brain into an epileptic brain (epileptogenesis) as well as the processes which generate individual seizures (ictogenesis) may necessitate broadening our focus to other cell types. As will be detailed in this review, astrocytes augment neuronal activity at the level of individual neurons in the form of gliotransmission and the tripartite synapse. Under normal conditions, astrocytes are essential to the maintenance of blood-brain barrier integrity and remediation of inflammation and oxidative stress, but in epilepsy these functions are impaired. Epilepsy results in disruptions in the way astrocytes relate to each other by gap junctions which has important implications for ion and water homeostasis. In their activated state, astrocytes contribute to imbalances in neuronal excitability due to their decreased capacity to take up and metabolize glutamate and an increased capacity to metabolize adenosine. Furthermore, due to their increased adenosine metabolism, activated astrocytes may contribute to DNA hypermethylation and other epigenetic changes that underly epileptogenesis. Lastly, we will explore the potential explanatory power of these changes in astrocyte function in detail in the specific context of the comorbid occurrence of epilepsy and Alzheimer's disease and the disruption in sleep-wake regulation associated with both conditions. 


National Institutes of Health (NIH) through grants NS103740, NS065957, NS127846, NS117792

US Department of the Army through contract W81XWH2210638

Catalyst award from CURE Epilepsy

EpiPurines grant 101032321 from the European Commission



The original article is available at

Published Citation

Purnell BS, Alves M, Boison D. Astrocyte-neuron circuits in epilepsy. Neurobiol Dis. 2023;179:106058

Publication Date

1 March 2023

PubMed ID



  • Physiology and Medical Physics




  • Published Version (Version of Record)