ArticleProceedings of the National Academy of Sciences of the United States of America2013
Mammalian target of rapamycin complex 1 activation negatively regulates Polo-like kinase 2-mediated homeostatic compensation following neonatal seizures.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Cell-Intrinsic Regulation of Epilepsy-Associated Pathology by mTORC1 and mTORC2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Low expression of polo-like kinase 2 predicts high postoperative seizure recurrence in glioma-related epilepsy.American journal of translational research · 2025Article
- Reversible synaptic adaptations in a subpopulation of murine hippocampal neurons following early-life seizures.The Journal of clinical investigation · 2024Article
- Polo-Like Kinase 2: From Principle to Practice.Frontiers in oncology · 2022Review
- Dysregulation of GABAA Receptor-Mediated Neurotransmission during the Auditory Cortex Critical Period in the Fragile X Syndrome Mouse Model.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- mTOR-driven neural circuit changes initiate an epileptogenic cascade.Progress in neurobiology · 2021Article
- Impaired State-Dependent Potentiation of GABAergic Synaptic Currents Triggers Seizures in a Genetic Generalized Epilepsy Model.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Early life stress facilitates synapse premature unsilencing to enhance AMPA receptor function in the developing hippocampus.Journal of neurophysiology · 2020Article
- Developmentally Regulated Rebound Depolarization Enhances Spike Timing Precision in Auditory Midbrain Neurons.Frontiers in cellular neuroscience · 2020Article
- Inhibition of Polo-like kinase 2 ameliorates pathogenesis in Alzheimer's disease model mice.PloS one · 2019Article
- Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity.Cell reports · 2018Article
- Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease.Scientific reports · 2018Article
- What goes up must come down: homeostatic synaptic plasticity strategies in neurological disease.Future neurology · 2018Review
- Early-life seizures alter synaptic calcium-permeable AMPA receptor function and plasticity.Molecular and cellular neurosciences · 2016Article
- Cdk5 is a New Rapid Synaptic Homeostasis Regulator Capable of Initiating the Early Alzheimer-Like Pathology.Cerebral cortex (New York, N.Y. : 1991) · 2016Article
- Bortezomib alleviates drug-induced liver injury by regulating CYP2E1 gene transcription.International journal of molecular medicine · 2016Article
- Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons.Frontiers in cellular neuroscience · 2015Article
- Mechanisms regulating neuronal excitability and seizure development following mTOR pathway hyperactivation.Frontiers in molecular neuroscience · 2014Review
- AMPA receptor antagonist NBQX attenuates later-life epileptic seizures and autistic-like social deficits following neonatal seizures.Epilepsia · 2013Article
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4 authors at 2 institutions in 1 country.
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Abstract
Homeostatic plasticity is characterized by compensatory changes in synaptic strength and intrinsic membrane properties in response to chronic changes in neuronal activity. Neonatal seizures are a naturally occurring source of neuronal overactivation and can lead to long-term epilepsy and cognitive deficits. Using a rodent model of hypoxia-induced neonatal seizures that results in a persistent increase in AMPA receptor (AMPAR) function in hippocampal CA1 pyramidal neurons, we aimed to determine whether there was any evidence of an opposing endogenous homeostatic antiepileptic response. Given that this model results in long-term epilepsy, we also examined mechanisms whereby this homeostasis fails. Whole-cell patch-clamp recordings from neurons in slices removed at intervals following seizure onset revealed an initial up-regulation of AMPAR function that was followed by a transient dynamic attenuation of this enhancement by 48-72 h, although AMPAR function was still increased compared with nonseizure control baseline. This secondary down-regulation of enhanced AMPAR function was coincident with a marked transient increase in expression and function of the Polo-like kinase 2 (PLK2), which has previously been implicated in homeostatic down-regulation of neuronal excitability in cell/slice culture models. The effects were transient and at 1 wk AMPAR function once again became up-regulated, simultaneous with a decrease in PLK2 expression and function. This negative regulation was mediated by subacute postseizure increases in mammalian target of rapamycin (mTOR). Application of the mTOR inhibitor rapamycin prevented post-hypoxic seizure impairment of homeostasis, suggesting that homeostatic plasticity mechanisms may be potentially modifiable therapeutic targets in epileptogenesis.
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