Search bioRxivSearch

Biology subjects

Migaud, M.

Publications and source records attributed to Migaud, M..

3 recordsLinked to original sources

The sheep brain: an interesting translational model for functional MRI studies?

Biomedical investigations in clinically relevant animal models is of crucial interest for faster and appropriate transfer to human. The ovine model has already demonstrated its potential compared to rodents and non-human primates (NHP) in various studies: sheep possess a gyrencephalic brain, captivity is not an issue and can undergo magnetic resonance imaging (MRI) in routine clinical scanners (1.5T, 3T) under identical conditions using similar techniques to humans. To date, the effects of anesthesia have been poorly explored and only few functional MRI (fMRI) studies were conducted in sheep. Here, Blood Oxygen Level dependent fMRI and perfusion MRI were conducted in lambs and adult ewes at 3 T. Robust but weak BOLD responses to visual stimulation were found in the lateral geniculate nucleus (LGN) up to 3% isoflurane anaesthesia. BOLD responses were weaker in adult sheep than in lambs while relative cerebral blood volumes (rCBV) and relative cerebral blood flows (rCBF) were significantly higher in lambs than in adult sheep for both gray and white matter in accordance with previous findings in the human. Assessment of functional responses in healthy individuals under adequate physiological conditions is essential for robust translational studies.

neuroscience

Detection of homozygous and hemizygous partial exon deletions by whole-exome sequencing

The detection of copy number variations (CNVs) in whole-exome sequencing (WES) data is important, as CNVs may underlie a number of human genetic disorders. The recently developed HMZDelFinder algorithm can detect rare homozygous and hemizygous (HMZ) deletions in WES data more effectively than other widely used tools. Here, we present HMZDelFinder_opt, an approach that outperforms HMZDelFinder for the detection of HMZ deletions, including partial exon deletions in particular, in typical laboratory cohorts that are generated over time under different experimental conditions. We show that using an optimized reference control set of WES data, based on a PCA-derived Euclidean distance for coverage, strongly improves the detection of HMZ deletions both in real patients carrying validated disease-causing deletions and in simulated data. Furthermore, we develop a sliding window approach enabling HMZDelFinder-opt to identify HMZ partial deletions of exons that are otherwise undiscovered by HMZDelFinder. HMZDelFinder_opt is a timely and powerful approach for detecting HMZ deletions, particularly partial exon deletions, in laboratory cohorts, which are typically heterogeneous.

bioinformatics

Brain orchestration of pregnancy and maternal behavior in mice.

Reproduction induces changes within the brain to prepare for gestation and motherhood. However, the dynamic of these central changes and their relationships with the development of maternal behavior remain poorly understood. Here, we describe a longitudinal morphometric neuroimaging study in female mice between pre-gestation and weaning, using new magnetic resonance imaging (MRI) resources comprising a high-resolution brain template, its associated tissue priors (60-m isotropic resolution) and a corresponding mouse brain atlas (1320 regions of interest). Using these tools, we observed transient hypertrophies not only within key regions controlling gestation and maternal behavior (medial preoptic area, bed nucleus of the stria terminalis), but also in the amygdala, caudate nucleus and hippocampus. Additionally, unlike females exhibiting lower levels of maternal care, highly maternal females developed transient hypertrophies in somatosensory, entorhinal and retrosplenial cortices among other regions. Therefore, coordinated and transient brain modifications associated with maternal performance occurred during gestation and lactation.

neuroscience