Biology subjects

Mallard, C.

Publications and source records attributed to Mallard, C..

4 recordsLinked to original sources

bioRxiv2025

A Novel Framework for Quantitative Analysis of Neuronal Primary Cilia in Brain Tissue

BackgroundAccurate analysis of neuronal primary cilia is essential for understanding developmental processing of neurons. But existing image segmentation methods struggle with staining variability and background noise. To address this, we developed a more robust segmentation and statistical analysis pipeline using an animal model small sample size and with known neuronal microstructure alterations. MethodsMaternal obesity was induced in mice via a high-fat/high-sucrose diet. Hippocampal tissue from 6-month-old offspring of obese and control dams was analyzed. We developed a MATLAB-based pipeline to segment neuronal cilia from z-stack images, applying mathematical transformations and using the Weibull distribution and Bayesian Information Criterion (BIC) to assess group differences ResultsThe technique segmented cilia despite artifacts, revealing group-specific patterns. Statistical analysis confirmed significant differences, highlighting the methods robustness over traditional tests, especially with small samples. ConclusionOur method reliably segments neuronal primary cilia in immune-stained sections with thionin-counter staining and offers a sensitive, assumption-free alternative to traditional statistical tests, ideal for small-sample neurobiological studies

neuroscience↗

bioRxiv2024

Maternal n-3 enriched diet reprograms neurovascular transcriptome and blunts inflammation in neonate

Infection during perinatal period can adversely affect brain development, predispose infants to ischemic stroke and have lifelong consequences. We previously demonstrated that diet enriched in n-3 polyunsaturated fatty acids (PUFA) transforms brain lipid composition and protects from neonatal stroke. Vasculature is a critical interface between blood and brain providing a barrier to systemic infection. Here we examined whether maternal PUFA-enriched diets exert reprograming of endothelial cell signalling in 9-day old mice after endotoxin (LPS)-induced infection. Transcriptome analysis was performed on brain microvessels from pups born to dams maintained on 3 diets: standard, n-3 or n-6 enriched. N-3 diet enabled higher immune reactivity in brain vasculature, while preventing imbalance of cell cycle regulation and extracellular matrix cascades that accompanied inflammatory response in standard diet. LPS response in blood and brain was blunted in n-3 offspring. Cerebral angioarchitecture analysis revealed modified vessel complexity after LPS. Thus, n-3-enriched maternal diet partially prevents imbalance in homeostatic processes and alters inflammation rather than affects brain vascularization during early life. Importantly, maternal diet may presage offspring neurovascular outcomes later in life.

neuroscience↗

bioRxiv2022

Transcriptome network analysis link perinatal Staphylococcus epidermidis infection to microglia reprogramming in the immature hippocampus

Staphylococcus epidermidis (S. epidermidis) is the most common nosocomial pathogen in preterm infants and associated with increased risk of cognitive delay, however, underlying mechanisms are unknown. We employed morphological, transcriptomic and physiological methods to extensively characterize microglia in the immature hippocampus following S. epidermidis infection. 3D morphological analysis revealed activation of microglia after S. epidermidis. Differential expression combined with network analysis identified NOD-receptor signalling and trans-endothelial leukocyte trafficking as major mechanisms in microglia. In support, active caspase-1 was increased in the hippocampus and using the LysM-eGFP knock-in transgenic mouse, we demonstrate infiltration of leukocytes to the brain together with disruption of the blood-brain barrier. Our findings identify activation of microglia inflammasome as a major mechanism underlying neuroinflammation following infection. The results demonstrate that neonatal S. epidermidis infection share analogies with S. aureus and neurological diseases, suggesting a previously unrecognized important role in neurodevelopmental disorders in preterm born children.

neuroscience↗

bioRxiv2021

Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy

AimGrowth differentiation factor 15 (GDF15) increases in serum during pregnancy to levels not seen in any other physiological state and is suggested to be involved in pregnancy-induced nausea, weight regulation and glucose metabolism. The main action of GDF15 is regulated through a receptor of the brainstem, i.e., through exposure of GDF15 in both blood and cerebrospinal fluid (CSF). The aim of the current study was to measure GDF15 in both CSF and serum during pregnancy, and to compare it longitudinally to non-pregnant levels. MethodsWomen were sampled at elective caesarean section (n=45, BMI=28.1{+/-}5.0) and were followed up 5 years after pregnancy (n=25). GDF15, insulin and leptin were measured in CSF and serum. In addition, glucose, adiponectin and Hs-CRP were measured in blood. ResultsGDF15 levels were higher during pregnancy compared with follow-up in both CSF (385{+/-}128 vs. 115{+/-}32 ng/l, p<0.001) and serum (73789{+/-}29198 vs. 404{+/-}102 ng/l, p<0.001). CSF levels correlated with serum levels during pregnancy (p<0.001), but not in the non-pregnant state (p=0.98). Both CSF and serum GDF15 were highest in women carrying a female fetus (p<0.001), previously linked to pregnancy-induced nausea. Serum GDF15 correlated with the homeostatic model assessment for beta-cell function and placental weight, and CSF GDF15 correlated inversely with CSF insulin levels. ConclusionThis, the first study to measure CSF GDF15 during pregnancy, demonstrated increased GDF15 levels in both serum and CSF during pregnancy. The results suggest that effects of GDF15 during pregnancy can be mediated by increases in both CSF and serum levels.

physiology↗