Biology subjects

Sibilia, F.

Publications and source records attributed to Sibilia, F..

4 recordsLinked to original sources

bioRxiv2025

Exploring the association between walking, sleep patterns, brain perivascular spaces, and cognitive function in Parkinson's disease

Perivascular spaces (PVSs) support brain waste clearance and are influenced by sleep. In Parkinsons disease (PD), sleep is often disrupted, and can co-occur with gait dysfunction. This study investigated how sleep disruption, walking difficulties, and cognition relate in PD, considering PVS as a mediator. Our cohort included 348 participants -healthy controls (HC, n=59), prodromal (n=117), and PD patients (n=172)-in the Parkinsons Progression Markers Initiative (PPMI) study. Insomnia and walking issues were assessed by questionnaire, cognition was measured with the Symbol Digit Modalities (SDM) test, and PVS volume fraction in white matter (WM-PVS) and basal ganglia (BG-PVS) was quantified. PVS did not mediate the relationship between sleep or motor problems, on cognition. Walking difficulties were directly linked to poorer cognition, and insomnia to walking deficits. BG-PVS was negatively associated with cognition. PVS burden predicted cognitive function after five years, but not disease progression as indexed by cerebro-spinal fluid (CSF) biomarkers. These findings suggest walking deficits directly relate with cognition in PD, but the relationship is not mediated by PVS.

neuroscience↗

bioRxiv2023

Perivascular spaces in Alzheimer's disease are associated with inflammatory, stress-related, and hypertension biomarkers

Perivascular spaces (PVS) are fluid-filled spaces surrounding the brain vasculature. Literature suggests that PVS may play a significant role in aging and neurological disorders, including Alzheimers disease (AD). Cortisol, a stress hormone, has been implicated in the development and progression of AD. Hypertension, a common condition in older adults, has been found to be a risk factor for AD. Hypertension may contribute to PVS enlargement, impairing the clearance of waste products from the brain and promoting neuroinflammation. This study aims to understand the potential interactions between PVS, cortisol, hypertension, and inflammation in the context of cognitive impairment. Using MRI scans acquired at 1.5T, PVS were quantified in a cohort of 465 individuals with cognitive impairment. PVS was calculated in the basal ganglia and centrum semiovale using an automated segmentation approach. Levels of cortisol and angiotensin-converting enzyme (ACE) (an indicator of hypertension) were measured from plasma. Inflammatory biomarkers, such as cytokines and matrix metalloproteinases, were analyzed using advanced laboratory techniques. Main effect and interaction analyses were performed to examine the associations between PVS severity, cortisol levels, hypertension, and inflammatory biomarkers. In the centrum semiovale, higher levels of inflammation reduced cortisol associations with PVS volume fraction. For ACE, an inverse association with PVS was seen only when interacting with TNFr2 (a transmembrane receptor of TNF). There was also a significant inverse main effect of TNFr2. In the PVS basal ganglia, a significant positive association was found with TRAIL (a TNF receptor inducing apoptosis). These findings show for the first time the intricate relationships between PVS structure and the levels of stress-related, hypertension, and inflammatory biomarkers. This research could potentially guide future studies regarding the underlying mechanisms of AD pathogenesis and the potential development of novel therapeutic strategies targeting these inflammation factors.

neuroscience↗

bioRxiv2021

Age Differences in Diffusivity in the Locus Coeruleus and its Ascending Noradrenergic Tract

The noradrenergic locus coeruleus (LC) is a small brainstem nucleus that promotes arousal and attention. Recent studies have examined the microstructural properties of the LC using diffusion-weighted magnetic resonance imaging and found unexpected age-related differences in fractional anisotropy - a measure of white matter integrity. Here, we used three datasets (Berlin Aging Study-II, N = 301, the Leipzig Study for Mind-Body-Emotion Interactions, N = 220, and Stockholm Sleepy Brain, N = 49), to replicate published findings and expand them by investigating diffusivity in the LCs ascending noradrenergic bundle. In younger adults, LC fractional anisotropy was significantly lower, compared to older adults. However, in the LCs ascending noradrenergic bundle, we observed significantly higher fractional anisotropy in younger adults, relative to older adults. These findings indicate that diffusivity in the LC versus the ascending noradrenergic bundle are both susceptible to microstructural changes in aging that have opposing effects on fractional anisotropy. HighlightsO_LIFractional anisotropy in the locus coeruleus was lower in younger adults C_LIO_LIFractional anisotropy in the noradrenergic bundle was higher in younger adults C_LIO_LISleep deprivation may affect diffusivity in younger adults more than older adults C_LI

neuroscience↗

bioRxiv2019

Targeting the Administration of Ecdysterone in Doping Control Samples

PurposeThe phytosteroid ecdysterone was recently reported to enhance performance in sports and may thus be considered as a substance of relevance in anti-doping control. To trace back an administration of ecdysterone from urine samples analytical properties have been investigated to assess its integration into initial testing procedures (ITP) in doping control laboratories.\n\nMethodsAnalytical properties of ecdysterone were evaluated using GC-QTOF-MS and LC-QTOF-MS. Its metabolism and elimination in human were studied using urines collected after administration.\n\nResultsThe detectability of ecdysterone by GC-MS (after derivatization) and/or LC-MS(/MS) has been demonstrated and sample preparation methods were evaluated. Dilute-and-inject for LC-MS(/MS) or SPE using Oasis HLB for GC-MS or LC-MS were found most suitable, while liquid-liquid extraction was hampered by the high polarity of ecdysteroids.\n\nMost abundantly, ecdysterone was detected in the post administration urines as parent compound besides the metabolite desoxy-ecdysterone. Additionally desoxy-poststerone was tentatively assigned as minor metabolite, however further investigations are needed.\n\nConclusionAn administration of ecdysterone can be targeted using existing procedures of anti-doping laboratories. Ecdysterone and desoxy-ecdysterone appeared as suitable candidates for integration in ITP. Using dilute-and-inject a detection of the parent compound was possible for more than two days after the administration of a single dose of ~50 mg.

pharmacology and toxicology↗