Biology subjects

Rektorova, I.

Publications and source records attributed to Rektorova, I..

4 recordsLinked to original sources

bioRxiv2026

EEG dynamics in Lewy body diseases is related to clinical fluctuations and degeneration of locus coeruleus

This work investigates aperiodic bursts of neuronal activity, referred to as neuronal avalanches, which are thought to support flexible information processing in Lewy body (LB) disease. We compared avalanche-derived features across LB disease phenotypes (prodromal dementia with LB and Parkinsons disease, PD), with healthy controls (HC). Based on the premise that focal neurodegeneration alters whole-brain dynamics, we examined whether the "richness" of braindynamics was associated with clinical symptoms and with the microstructural integrity of catecholaminergic nuclei - the right caudal locus coeruleus (rcLC) and the substantia nigra pars compacta (SNpc). The sample comprised 30 HC, 56 cognitively normal individuals with core clinical features of dementia with LB (CN-CCF), 34 individuals with mild cognitive impairment with LB (MCI-LB), and 30 advanced PD patients. Neuronal avalanches were extracted from source-reconstructed resting-state EEG and described by their count, the number of unique spatial patterns (flexibility), hemispheric symmetry of flexibility, and avalanche transition matrices. LC and SNpc integrity were assessed using neuromelanin-sensitive MRI and free-water diffusion imaging, respectively. Lewy body disease groups exhibited increased flexibility relative to HC, which was, in prodromal groups, associated with cognitive fluctuations and REM sleep behavior disorder symptoms, but not parkinsonism. Flexibility was negatively related to rcLC integrity, which was lowest in MCI-LB. These findings suggest that elevated flexibility reflects dysregulated brain dynamics linked to malignant non-motor features of LB diseases and to the caudal LC involvement.

neuroscience↗

bioRxiv2025

A 'brain-first' mouse model of progressive alpha-synuclein pathology via intranasal rotenone administration

The precise aetiology of Parkinsons disease (PD) is still poorly understood, but it is thought to arise due to an intricate relationship between genes and the environment. Our study takes a unique approach to understanding the effect of environmental factors on the onset and progression of -synuclein (aSyn) pathology, a key feature of PD, from the olfactory bulb (OB) to other brain regions. In the present study, we evaluated the time-dependent progression of PD-like pathology by administering rotenone intranasally for 5.5 months in C57BL/6 male mice. We performed olfactory and motor tests and examined the aSyn accumulation, glial cell activation and dopaminergic neurodegeneration after 3, 4 and 5.5 months of rotenone exposure by immunoblotting and immunofluorescence techniques. We observed a time-dependent progression of aSyn accumulation from the OB to other brain regions, including the mid-brain and cortex. Consistently, we observed a time-dependent behavioural impairment, OB atrophy, progression of aSyn pathology, neuroinflammation and neurodegeneration. Our findings also established a link between distinct astrocyte activation and dopaminergic (DAergic) activity. In conclusion, this chronic and progressive mouse model mimics the brain-first type of progression of PD-like pathology in some PD patients, opening the possibility for testing potential disease-modifying interventions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/677764v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@5a983eorg.highwire.dtl.DTLVardef@1c115ceorg.highwire.dtl.DTLVardef@17eb778org.highwire.dtl.DTLVardef@3f3fa4_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

PPM1M, a LRRK2-counteracting, phosphoRab12-preferring phosphatase with potential link to Parkinsons disease

Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases that regulate receptor trafficking; activating mutations in LRRK2 are linked to Parkinsons disease. Rab phosphorylation is a transient event that can be reversed by phosphatases, including PPM1H, that acts on phosphoRab8A and phosphoRab10. Here we report a phosphatome-wide siRNA screen that identified PPM1M as a phosphoRab12-preferring phosphatase that also acts on phosphoRab8A and phosphoRab10. Upon knockout from cells or mice, PPM1M displays selectivity for phosphoRab12. As shown previously for mice harboring LRRK2 pathway mutations, knockout of Ppm1m leads to primary cilia loss in striatal cholinergic interneurons. We have also identified a rare PPM1M mutation in patients with Parkinsons disease that is catalytically inactive when tested in vitro and in cells. These findings identify PPM1M as a key player in the LRRK2 signaling pathway and provide a new therapeutic target for the possible benefit of patients with Parkinsons disease. TeaserParkinsons linked Rab phosphorylation is reversed by PPM1M; the inactive D440N variant is implicated in rare patient cases.

cell biology↗

bioRxiv2018

Small effect size leads to reproducibility failure in resting-state fMRI studies

Thousands of papers using resting-state functional magnetic resonance imaging (RS-fMRI) have been published on brain disorders. Results in each paper may have survived correction for multiple comparison. However, since there have been no robust results from large scale meta-analysis, we do not know how many of published results are truly positives. The present meta-analytic work included 60 original studies, with 57 studies (4 datasets, 2266 participants) that used a between-group design and 3 studies (1 dataset, 107 participants) that employed a within-group design. To evaluate the effect size of brain disorders, a very large neuroimaging dataset ranging from neurological to psychiatric isorders together with healthy individuals have been analyzed. Parkinsons disease off levodopa (PD-off) included 687 participants from 15 studies. PD on levodopa (PD-on) included 261 participants from 9 studies. Autism spectrum disorder (ASD) included 958 participants from 27 studies. The meta-analyses of a metric named amplitude of low frequency fluctuation (ALFF) showed that the effect size (Hedges g) was 0.19 - 0.39 for the 4 datasets using between-group design and 0.46 for the dataset using within-group design. The effect size of PD-off, PD-on and ASD were 0.23, 0.39, and 0.19, respectively. Using the meta-analysis results as the robust results, the between-group design results of each study showed high false negative rates (median 99%), high false discovery rates (median 86%), and low accuracy (median 1%), regardless of whether stringent or liberal multiple comparison correction was used. The findings were similar for 4 RS-fMRI metrics including ALFF, regional homogeneity, and degree centrality, as well as for another widely used RS-fMRI metric namely seed-based functional connectivity. These observations suggest that multiple comparison correction does not control for false discoveries across multiple studies when the effect sizes are relatively small. Meta-analysis on un-thresholded t-maps is critical for the recovery of ground truth. We recommend that to achieve high reproducibility through meta-analysis, the neuroimaging research field should share raw data or, at minimum, provide un-thresholded statistical images.

neuroscience↗