Astrocyte-neuron circuits in epilepsy
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 inhibiti...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-04-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123000724 |
| _version_ | 1827987045195186176 |
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| author | Benton S. Purnell Mariana Alves Detlev Boison |
| author_facet | Benton S. Purnell Mariana Alves Detlev Boison |
| author_sort | Benton S. Purnell |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T23:40:47Z |
| format | Article |
| id | doaj.art-a9f57acfcf684ef5a89bdeabb0c62cd0 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-09T23:40:47Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-a9f57acfcf684ef5a89bdeabb0c62cd02023-03-19T04:37:10ZengElsevierNeurobiology of Disease1095-953X2023-04-01179106058Astrocyte-neuron circuits in epilepsyBenton S. Purnell0Mariana Alves1Detlev Boison2Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, United States of AmericaDepartment of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, United States of America; Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin D02 YN77, IrelandDepartment of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, United States of America; Brain Health Institute, Rutgers University, Piscataway, NJ, United States of America; Corresponding author at: Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, 683 Hoes Lane West, Piscataway, NJ 08854, United States of America.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.http://www.sciencedirect.com/science/article/pii/S0969996123000724AstrocytesGliaMetabolismEpilepsyAdenosineTherapy |
| spellingShingle | Benton S. Purnell Mariana Alves Detlev Boison Astrocyte-neuron circuits in epilepsy Neurobiology of Disease Astrocytes Glia Metabolism Epilepsy Adenosine Therapy |
| title | Astrocyte-neuron circuits in epilepsy |
| title_full | Astrocyte-neuron circuits in epilepsy |
| title_fullStr | Astrocyte-neuron circuits in epilepsy |
| title_full_unstemmed | Astrocyte-neuron circuits in epilepsy |
| title_short | Astrocyte-neuron circuits in epilepsy |
| title_sort | astrocyte neuron circuits in epilepsy |
| topic | Astrocytes Glia Metabolism Epilepsy Adenosine Therapy |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123000724 |
| work_keys_str_mv | AT bentonspurnell astrocyteneuroncircuitsinepilepsy AT marianaalves astrocyteneuroncircuitsinepilepsy AT detlevboison astrocyteneuroncircuitsinepilepsy |