This study aimed to determine the long-term change of seizure susceptibility and the role of nNOS on brain development following recurrent early-life seizures in rats. Video-EEG recordings were conducted between postnatal days 50 and 60. Alterations in seizure susceptibility were assayed on day 22 or 50 using the flurothyl method. Changes in nNOS expression were determined by quantitative immunoblotting on day 50. On average, rats had 8.4+/-2.7 seizures during 10 daily 1 hr behavioral monitoring sessions. As adults (days 50-60), all rats displayed interictal spikes in the hippocampus and/or overlying cortex. Brief electrographic seizures were recorded in only one of five animals. Rats appeared to progress from a period of marked seizure susceptibility (day 22) to one of lessened seizure susceptibility (day 50). Up-regulation of nNOS expression following early-life recurrent seizures was observed on day 50. In conclusion, these data suggested that recurrent early-life seizures had the long-term effects on seizure susceptibility late in life and up-regulatory nNOS expression on the hippocampus during brain development, and nNOS appeared to contribute to the persistent changes in seizure susceptibility, and epileptogenesis.
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http://dx.doi.org/10.3346/jkms.2010.25.6.905 | DOI Listing |
Unlabelled: SYNGAP1 is a key Ras-GAP protein enriched at excitatory synapses, with mutations causing intellectual disability and epilepsy in humans. Recent studies have revealed that in addition to its role as a negative regulator of G-protein signaling through its GAP enzymatic activity, SYNGAP1 plays an important structural role through its interaction with post-synaptic density proteins. Here, we reveal that intrinsic excitability deficits and seizure phenotypes in heterozygous Syngap1 knockout (KO) mice are differentially dependent on Syngap1 GAP activity.
View Article and Find Full Text PDFBackground And Purpose: Polycystins (PKD2, PKD2L1) are voltage-gated and Ca -modulated members of the transient receptor potential (TRP) family of ion channels. Loss of PKD2L1 expression results in seizure-susceptibility and autism-like features in mice, whereas variants in PKD2 cause autosomal dominant polycystic kidney disease. Despite decades of evidence clearly linking their dysfunction to human disease and demonstrating their physiological importance in the brain and kidneys, the polycystin pharmacophore remains undefined.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Integrative Biology & Physiology, University of California, Los Angeles, CA, USA.
The gut microbiome modulates the anti-seizure effects of the ketogenic diet, but how specific dietary formulations differentially modify the gut microbiome in ways that impact seizure outcome is poorly understood. We find that medical ketogenic infant formulas vary in macronutrient ratio, fat source, and fiber content and differentially promote resistance to 6-Hz seizures in mice. Dietary fiber, rather than fat ratio or source, drives substantial metagenomic shifts in a model human infant microbial community.
View Article and Find Full Text PDFCNS Drugs
January 2025
Division of Pharmacology, Department of Neuroscience, University of Naples "Federico II", Naples, Italy.
Voltage-gated Kv7 potassium channels, particularly Kv7.2 and Kv.7.
View Article and Find Full Text PDFHum Mol Genet
January 2025
Department of Human Genetics, Inselspital Bern, University of Bern, Freiburgstrasse 15, Bern 3010, Switzerland.
While de novo missense variants in the BTB domains of atypical RhoGTPase RHOBTB2 cause a severe developmental and epileptic encephalopathy, de novo missense variants in the GTPase domain or bi-allelic truncating variants are associated with more variable neurodevelopmental and seizure phenotypes. Apart from the observation of RHOBTB2 abundance resulting from BTB-domain variants and increased seizure susceptibility in Drosophila overexpressing RhoBTB, our knowledge on RHOBTB2-related pathomechanisms is limited. We now found enrichment for ion channels among the differentially expressed genes from RNA-Seq on fly heads overexpressing RhoBTB.
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