ArticleEpilepsia2021
Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity.
Article in Epilepsia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Revisiting gut microbiota-driven ammonia metabolism: from disease burden to physiological adaptation.Gut microbes · 2026Review
- Silymarin Reverses Seizure-Precipitating Effects of Alcohol and Associated Psychiatric Comorbidities, and Neurotoxicity in Pentylenetetrazol Pre-Kindled Mice.Neurotoxicity research · 2026Article
- Single cell multiomic landscape reveals gene programs driving lipid droplet heterogeneity in hepatic steatosis.Scientific reports · 2026Article
- Antiepileptic and Neuroprotective Biochemical Actions of Sabinene Prevent the Development of Pentylenetetrazol-Induced Seizures and Neuropsychiatric Comorbidities in Mice.Journal of molecular neuroscience : MN · 2025Article
- Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity.Brain, behavior, and immunity · 2024Article
- Transient Impairment in Microglial Function Causes Sex-Specific Deficits in Synaptic and Hippocampal Function in Mice Exposed to Early Adversity.bioRxiv : the preprint server for biology · 2024Article
- Astrocytic pathology in Alpers' syndrome.Acta neuropathologica communications · 2023Article
- Glial Glutamine Homeostasis in Health and Disease.Neurochemical research · 2023Review
- Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism.Biomolecules · 2022Article
- Global trends in research of glutamate in epilepsy during past two decades: A bibliometric analysis.Frontiers in neuroscience · 2022Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe astroglial enzyme glutamine synthetase (GS) is deficient in small loci in the brain in adult patients with different types of focal epilepsy; however, the role of this deficiency in the pathogenesis of epilepsy has been difficult to assess due to a lack of sufficiently sensitive and specific animal models. The aim of this study was to develop an in vivo approach for precise and specific deletions of the GS gene in the postnatal brain.
methodsWe stereotaxically injected various adeno-associated virus (AAV)-Cre recombinase constructs into the hippocampal formation and neocortex in 22-70-week-old GS
resultsThe construct AAV8-glial fibrillary acidic protein-green fluorescent protein-Cre eliminated GS in >99% of astrocytes in the injection center with a gradual return to full GS expression toward the periphery. Such focal GS deletion reduced seizure threshold, caused spontaneous recurrent seizures, and diminished functional connectivity. SIGNIFICANCE: These results suggest that small loci of GS deficiency in the postnatal brain are sufficient to cause epilepsy and impaired functional connectivity. Additionally, given the high specificity and precise spatial resolution of our GS knockdown approach, we anticipate that this model will be extremely useful for rigorous in vivo and ex vivo studies of astroglial GS function at the brain-region and single-cell levels.
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