ArticleNeuroscience2012
Rapamycin down-regulates KCC2 expression and increases seizure susceptibility to convulsants in immature rats.
Article in Neuroscience, 2012. 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, 34 citations in OpenAlex.
- KCC2 activation during postnatal development alleviates long-term deficits in CDKL5-deficient mice.Experimental & molecular medicine · 2026Article
- Review
- Scoping review of disease-modifying effect of drugs in experimental epilepsy.Frontiers in neurology · 2023Article
- Shared mechanisms of neural circuit disruption in tuberous sclerosis across lifespan: Bridging neurodevelopmental and neurodegenerative pathology.Frontiers in genetics · 2022Review
- Efficacy of the Ketogenic Diet for Pediatric Epilepsy According to the Presence of Detectable Somatic mTOR Pathway Mutations in the Brain.Journal of clinical neurology (Seoul, Korea) · 2022Article
- Analysis of intraoperative human brain tissue transcriptome reveals putative risk genes and altered molecular pathways in glioma-related seizures.Epilepsy research · 2021Article
- Insights into Potential Targets for Therapeutic Intervention in Epilepsy.International journal of molecular sciences · 2020Review
- Microglial mTOR is Neuronal Protective and Antiepileptogenic in the Pilocarpine Model of Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Therapeutic role of targeting mTOR signaling and neuroinflammation in epilepsy.Epilepsy research · 2020Review
- [Correlation of phosphorylated S6 protein expression in blood and brain tissue in mice and rats with kainic acid-induced seizure].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2019Article
- M-Calpain Activation Facilitates Seizure Induced KCC2 Down Regulation.Frontiers in molecular neuroscience · 2018Article
- Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- mTOR referees memory and disease through mRNA repression and competition.FEBS letters · 2017Review
- mTORC1 Is a Local, Postsynaptic Voltage Sensor Regulated by Positive and Negative Feedback Pathways.Frontiers in cellular neuroscience · 2017Article
- Impact of rapamycin on status epilepticus induced hippocampal pathology and weight gain.Experimental neurology · 2016Article
- Non-invasive treatment options for focal cortical dysplasia.Experimental and therapeutic medicine · 2016Article
- Intermittent dosing of rapamycin maintains antiepileptogenic effects in a mouse model of tuberous sclerosis complex.Epilepsia · 2015Article
- Review
- Erythropoietin attenuates loss of potassium chloride co-transporters following prenatal brain injury.Molecular and cellular neurosciences · 2014Article
- Pathophysiogenesis of mesial temporal lobe epilepsy: is prevention of damage antiepileptogenic?Current medicinal chemistry · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Seizure susceptibility to neurological insults, including chemical convulsants, is age-dependent and most likely reflective of overall differences in brain excitability. The molecular and cellular mechanisms underlying development-dependent seizure susceptibility remain to be fully understood. Because the mammalian target of rapamycin (mTOR) pathway regulates neurite outgrowth, synaptic plasticity and cell survival, thereby influencing brain development, we tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes seizure susceptibility to neurological insults. We found that inhibition of mTOR by rapamycin in immature rats (3-4 weeks old) increases the severity of seizures induced by pilocarpine, including lengthening the total seizure duration and reducing the latency to the onset of seizures. Rapamycin also reduces the minimal dose of pentylenetetrazol (PTZ) necessary to induce clonic seizures. However, in mature rats, rapamycin does not significantly change the seizure sensitivity to pilocarpine and PTZ. Likewise, kainate sensitivity was not significantly affected by rapamycin treatment in either mature or immature rats. Additionally, rapamycin treatment down-regulates the expression of potassium-chloride cotransporter 2 (KCC2) in the thalamus and to a lesser degree in the hippocampus. Pharmacological inhibition of thalamic mTOR or KCC2 increases susceptibility to pilocarpine-induced seizure in immature rats. Thus, our study suggests a role for the mTOR pathway in age-dependent seizure susceptibility.
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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.