ArticleGene therapy2016
DREADDs suppress seizure-like activity in a mouse model of pharmacoresistant epileptic brain tissue.
Article in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- The mechanism of parvalbumin interneurons regulating glutamatergic neurons involvement in stress induced anxiety in the basolateral amygdala of male mice.Scientific reports · 2025Article
- A minimally invasive, fast on/off "odorgenetic" method to manipulate physiology.Protein & cell · 2025Article
- Chemogenetics with PSAMGene therapy · 2025Article
- Parvalbumin Interneuron Dysfunction in Neurological Disorders: Focus on Epilepsy and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Cell-specific switch for epileptiform activity: critical role of interneurons in the mouse subicular network.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Chemogenetic attenuation of cortical seizures in nonhuman primates.Nature communications · 2023Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- DREADDs in Epilepsy Research: Network-Based Review.Frontiers in molecular neuroscience · 2022Review
- Chemogenetic Seizure Control with Clozapine and the Novel Ligand JHU37160 Outperforms the Effects of Levetiracetam in the Intrahippocampal Kainic Acid Mouse Model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures.Nature communications · 2021Article
- Chemogenetics: Beyond Lesions and Electrodes.Neurosurgery · 2021Review
- The Quest for the Hippocampal Memory Engram: From Theories to Experimental Evidence.Frontiers in behavioral neuroscience · 2020Review
- Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients.Scientific reports · 2019Article
- Designer receptor technology for the treatment of epilepsy.EBioMedicine · 2019Review
- "Are We There Yet?" Quest for Treatment of Refractory Epilepsy.Epilepsy currents · 2019Article
- Novel Optogenetic Approaches in Epilepsy Research.Frontiers in neuroscience · 2019Review
- Optogenetic dissection of ictogenesis: in search of a targeted anti-epileptic therapy.Journal of neural engineering · 2018Review
- Dynamic interaction of local and transhemispheric networks is necessary for progressive intensification of hippocampal seizures.Scientific reports · 2018Article
- Chemogenetic Recruitment of Specific Interneurons Suppresses Seizure Activity.Frontiers in cellular neuroscience · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epilepsy is a neurological disorder with a prevalence of ≈1% of general population. Available antiepileptic drugs (AEDs) have multiple side effects and are ineffective in 30% of patients. Therefore, development of effective treatment strategies is highly needed, requiring drug-screening models that are relevant and reliable. We investigated novel chemogenetic approach, using DREADDs (designer receptors exclusively activated by designer drugs) as possible inhibitor of epileptiform activity in organotypic hippocampal slice cultures (OHSCs). The OHSCs are characterized by increased overall excitability and closely resemble features of human epileptic tissue. Studies suggest that chemically induced epileptiform activity in rat OHSCs is pharmacoresistant to most of AEDs. However, high-frequency electric stimulus train-induced bursting (STIB) in OHSCs is responsive to carbamazepine and phenytoin. We investigated whether inhibitory DREADD, hM4Di, would be effective in suppressing STIB in OHSC. hM4Di is a mutated muscarinic receptor selectively activated by otherwise inert clozapine-N-oxide, which leads to hyperpolarization in neurons. We demonstrated that this hyperpolarization effectively suppresses STIB in mouse OHSCs. As we also found that STIB in mouse OHSCs is resistant to common AED, valproic acid, collectively our findings suggest that DREADD-based strategy may be effective in suppressing epileptiform activity in a pharamcoresitant epileptic brain tissue.
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