ArticleBrain : a journal of neurology2019
The role of astrocytes in seizure generation: insights from a novel in vitro seizure model based on mitochondrial dysfunction.
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
- Astrocytes in Genetic Epilepsies: Supporting Actor or Key Player?Journal of neuroscience research · 2026Review
- Apoptosis and Glial Marker Profiles in Hippocampus and Amygdala of Medically Intractable Temporal Lobe Epilepsy.Journal of cellular and molecular medicine · 2026Article
- The adhesion GPCR ADGRV1 controls glutamate homeostasis in hippocampal astrocytes supporting neurons.Acta neuropathologica communications · 2026Article
- The Biomarkers and Underlying Mechanisms of Mitochondrial and Programmed Cell Death Related Genes in Epilepsy by Combining Transcriptome and Single-Cell Sequencing.Journal of Korean Neurosurgical Society · 2026Article
- Inhibitory GABAergic Neuron Loss due to Oxidative Damage During Ex Vivo Acute Brain Slice Preparation Influences Genesis and Dynamics of Epileptiform Activity.Journal of neurochemistry · 2026Article
- Epileptogenesis and Epilepsy Treatment: Advances in Mechanistic Understanding, Therapeutic Approaches, and Future Perspectives.International journal of molecular sciences · 2026Review
- The interplay between metabolism and neuroinflammation in epilepsy: mechanisms and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Seizure evolution in a mouse model of West syndrome involves complex and time-dependent synapse remodeling, gliosis and alterations in lipid metabolism.PLoS biology · 2025Article
- Canine EEG helps human: cross-species and cross-modality epileptic seizure detection via multi-space alignment.National science review · 2025Article
- Delineating the mechanisms of cerebellar degeneration in paediatric and adult primary mitochondrial disease.Acta neuropathologica · 2025Article
- Metabolic aspects of genetic ion channel epilepsies.Journal of neurochemistry · 2024Review
- Mitochondria-related HSDL2 is a potential biomarker in temporal lobe epilepsy by modulating astrocytic lipid metabolism.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- pH regulating mechanisms of astrocytes: A critical component in physiology and disease of the brain.Cell calcium · 2024Review
- Delineating mechanisms underlying parvalbumin neuron impairment in different neurological and neurodegenerative disorders: the emerging role of mitochondrial dysfunction.Biochemical Society transactions · 2024Review
- Magnetic resonance spectroscopy in MELAS syndrome: correlation with CSF and plasma metabolite levels and change after glutamine supplementation.Neuroradiology · 2024Observational
- Combined transcriptomics and proteomics studies on the effect of electrical stimulation on spinal cord injury in rats.Heliyon · 2024Article
- Evidence for prodromal changes in neuronal excitability and neuroinflammation in the hippocampus in young alpha-synuclein (A30P) transgenic mice.Frontiers in dementia · 2024Article
- Neuron-Astrocyte Interactions: A Human Perspective.Advances in neurobiology · 2024Review
- Article
- Role ofFrontiers in molecular neuroscience · 2024Article
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Approximately one-quarter of patients with mitochondrial disease experience epilepsy. Their epilepsy is often severe and resistant towards conventional antiepileptic drugs. Despite the severity of this epilepsy, there are currently no animal models available to provide a mechanistic understanding of mitochondrial epilepsy. We conducted neuropathological studies on patients with mitochondrial epilepsy and found the involvement of the astrocytic compartment. As a proof of concept, we developed a novel brain slice model of mitochondrial epilepsy by the application of an astrocytic-specific aconitase inhibitor, fluorocitrate, concomitant with mitochondrial respiratory inhibitors, rotenone and potassium cyanide. The model was robust and exhibited both face and predictive validity. We then used the model to assess the role that astrocytes play in seizure generation and demonstrated the involvement of the GABA-glutamate-glutamine cycle. Notably, glutamine appears to be an important intermediary molecule between the neuronal and astrocytic compartment in the regulation of GABAergic inhibitory tone. Finally, we found that a deficiency in glutamine synthetase is an important pathogenic process for seizure generation in both the brain slice model and the human neuropathological study. Our study describes the first model for mitochondrial epilepsy and provides a mechanistic insight into how astrocytes drive seizure generation in mitochondrial epilepsy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.