Biology subjects

Prochazkova, N.

Publications and source records attributed to Prochazkova, N..

4 recordsLinked to original sources

bioRxiv2026

High-frequency oscillations reveal progressive recruitment of remote cortex into the epileptic network in a mouse model of focal cortical dysplasia type II

Interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs) are established biomarkers of epileptogenic tissue, but how their spatiotemporal evolution reflects epileptic network reorganization in neocortical epilepsy remains unclear. We investigated longitudinal IED and HFO dynamics throughout epileptogenesis and chronic epilepsy in a mouse model of focal cortical dysplasia type II (FCD II). Long-term bilateral cortical recordings were obtained before and after spontaneous seizure onset. IEDs and HFOs (gamma, ripples, and fast ripples) were quantified in the dysplastic lesion and contralateral cortex during pre-epileptic, early, and late epileptic stages. The dysplastic lesion remained the principal seizure onset zone throughout disease progression and showed stable HFO activity after epilepsy onset. In contrast, the contralateral cortex exhibited progressive increases in IEDs and HFOs, demonstrating continuous recruitment into the epileptic network. Fast ripples were the earliest marker of this process, emerging within the first week after the first seizure and preceding increases in ripples, gamma, and IEDs. Propagation analysis showed that this contralateral increase was driven by independently generated HFOs rather than propagation from the lesion, indicating emergence of autonomous epileptogenic activity outside the primary focus. Spatiotemporal HFO analysis thus captures dynamic epileptic network remodeling beyond epileptogenic lesion. Fast ripples may serve as an early signature of network expansion and epileptogenicity emerging outside the primary lesion. Widespread structural and connectivity abnormalities extending beyond the lesion, combined with intense recurrent epileptic activity, may underlie the high endogenous epileptogenicity of FCD II, enabling small dysplastic lesions to recruit extensive neuronal networks across both hemispheres.

neuroscience↗

bioRxiv2026

Dasatinib-Quercetin May Reduce Senescence Markers, Without Senolysis or Seizure Modification, in a Mouse Model of Focal Cortical Dysplasia

Mounting evidence from surgical type II focal cortical dysplasia (FCD) tissues and mouse models have recently shown that dysmorphic neurons carrying MTOR mutations (DNs) in FCD exhibit hallmarks of cellular senescence. Building on pioneering work from the Baulac group identifying cellular senescence as a feature of mTOR-pathway FCD, a recent study by Ribierre et al. (2024) [1] proposed oral dasatinib and quercetin (DQ) as a therapy that partially decreases the load of mutant, senescent neurons and thus reduces seizure occurrence in FCD mice. Using a different mouse strain and a different gain-of-function mutation in MTOR, our data confirm the presence of senescence hallmarks in FCD mice, but do not support one of the conclusions of Ribierre et al.--that DQ acts as a senolytic in an FCD mouse model--and we propose an alternative interpretation. We longitudinally tracked individual cell fate using two-photon microscopy and complemented these data with EEG monitoring and immunohistochemistry. Immunohistochemical analyses were performed within the same sections using multiple markers, allowing direct identification of mutant neurons and assessment of senescence-associated labeling. While we observed a detectable reduction in a senescence-associated marker, consistent with a senomorphic effect, it did not translate into a change in seizure phenotype, despite treatment timing and dosing matching those in the original study. For detailed materials and methods, see Extended Methods.

neuroscience↗

bioRxiv2025

SEIZURE OCCURRENCE IN FCD TYPE II IS PREDICTED BY LESION POSITION AND LINKED TO CYTOARCHITECTURAL ALTERATIONS

Focal cortical dysplasia (FCD) is a common malformation of cortical development and a major cause of early-onset, drug-resistant epilepsy. FCD type II is defined by abnormal lamination, altered cellular composition, and pathological cells, notably dysmorphic neurons (DNs) and balloon cells. DNs are thought to drive epileptogenicity through both cell-autonomous and non-cell-autonomous mechanisms, the latter including not only aberrant connectivity but also indirect modulation of excitability in local cell populations. We performed a multiscale structural and morphological analysis to elucidate the basis of FCD epileptogenicity and the impact of somatic mTOR mutations during brain development. Using a mouse model of FCD type II, we show that lesions in frontal and motor cortical regions are the strongest predictors of spontaneous seizure occurrence. This localization-dependent epileptogenicity offers an experimental explanation for the higher clinical epileptogenicity of frontal FCDs and suggests that posterior lesions may remain silent--an open question in human pathology. In our model, FCD tissue displayed considerable expansion, with cortical thickness up to [~]20% in seizure-bearing animals. This expansion coincided with an overall [~]40% reduction in neuronal density, consistent with tissue hypertrophy. DN density did not differ between seizure and non-seizure animals, challenging the notion that higher DN load directly predicts epileptogenesis. At the microscopic level, we describe DN axonal pathologies, including giant varicosities. In the cortex, these appeared as vesicle-filled boutons, whereas along callosal axons they were frequent but largely empty. Bouton density was markedly reduced in FCD cortex. Together, these findings leave the net synaptic effect of dysmorphic neurons unresolved, challenging the assumption that axonal hypertrophy translates into increased excitatory drive. While morphological abnormalities in FCD type II are well documented, their functional consequences remain incompletely understood. Here, we used macro- and microscopic structural features of FCDII to assess seizure susceptibility, providing new insights into epileptogenesis.

neuroscience↗

bioRxiv2024

Gut environmental factors explain variations in the gut microbiome composition and metabolism within and between healthy adults

The human gut microbiome is highly personal. However, the contribution of the gut environment to variations in the gut microbiome remains elusive. Here, we profiled the gut microbiome composition and metabolism over 9 consecutive days in 61 healthy adults and assessed gut environmental factors including segmental transit time and pH using a wireless motility capsule. Day-to-day fluctuations in gut environmental factors as well as segmental transit time and pH varied substantially between individuals. The gut environment explained more variations in gut microbiome and urine metabolome than dietary macronutrients or personal characteristics. Finally, we identified coffee-derived metabolites to be negatively correlated with small intestinal transit time and several microbial metabolites to be associated with colonic transit time including urinary proteolytic markers, faecal short-chain fatty acids, and breath methane. Our work suggests that the gut environment is key for understanding the individuality of the human gut microbiome composition and metabolism.

microbiology↗