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Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction

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TLDR
It is suggested that insights into the mechanisms of epileptogenesis converge at the level of cortical circuit dysfunction, with the hope of preventing epilepsy before seizures emerge.
Abstract
Epilepsy is a prevalent neurological disorder associated with significant morbidity and mortality, but the only available drug therapies target its symptoms rather than the underlying cause The process that links brain injury or other predisposing factors to the subsequent emergence of epilepsy is termed epileptogenesis Substantial research has focused on elucidating the mechanisms of epileptogenesis so as to identify more specific targets for intervention, with the hope of preventing epilepsy before seizures emerge Recent work has yielded important conceptual advances in this field We suggest that such insights into the mechanisms of epileptogenesis converge at the level of cortical circuit dysfunction

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Journal ArticleDOI

Microglial contributions to aberrant neurogenesis and pathophysiology of epilepsy.

TL;DR: The role of microglia post-seizure is still limited and may be pivotal in recognizing new therapeutic targets for seizure intervention, and insights into changes in neurogenesis and synaptic pruning are discovered in both health and disease.
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Environmental enrichment delays limbic epileptogenesis and restricts pathologic synaptic plasticity.

TL;DR: The hypothesis that environmental enrichment (EE) confers antiepileptogenic, psychoprotective, and neuroprotective effects in the amygdala kindling model of MTLE is tested and potential neurobiologic mechanisms are explored.
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(+)-Dehydrofukinone modulates membrane potential and delays seizure onset by GABAa receptor-mediated mechanism in mice.

TL;DR: The data indicate that DHF has anticonvulsant properties and the molecular target underlying this effect is likely to be the facilitation of GABAergic neuronal inhibition.
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Noise amplification precedes extreme epileptic events on human EEG

TL;DR: In this paper, the authors demonstrate that the time series of electroencephalogram (EEG) spectral power in a frequency band of 1-5 Hz obeys a heavy-tailed distribution, confirming the presence of extreme events.
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Chronic fluoxetine treatment accelerates kindling epileptogenesis in mice independently of 5-HT2A receptors

TL;DR: It is concluded that treatment with fluoxetine promotes epileptogenesis in mice, but this effect is not mediated by 5‐HT2A receptors, which suggests that antidepressants may accelerate the onset of acquired epilepsy in patients who have experienced epileptogenic cerebral insults.
References
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mTOR Signaling in Growth Control and Disease

TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.
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mTOR signaling in growth control and disease.

TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.
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Genome-Wide Mapping of in Vivo Protein-DNA Interactions

TL;DR: A large-scale chromatin immunoprecipitation assay based on direct ultrahigh-throughput DNA sequencing was developed, which was then used to map in vivo binding of the neuron-restrictive silencer factor (NRSF; also known as REST) to 1946 locations in the human genome.
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Driving fast-spiking cells induces gamma rhythm and controls sensory responses

TL;DR: The timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses and provided the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.
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