Biology subjects

Desco, M.

Publications and source records attributed to Desco, M..

5 recordsLinked to original sources

bioRxiv2022

Estimation of Vertex-wise Sulcal Width Maps on Cortical Surfaces

Sulcal width, defined as the physical distance between opposing sulcal banks, has shown promise as a biomarker. We present the first method to obtain a vertex-wise representation of this metric directly on the brains cortical surface. The algorithm samples the surface at different depths and estimates the distances between the opposing sulcal banks. The method is validated against a simulated sulcus and compared to other sulcal width tools based on regions of interest, showing solid correlations between the proposed algorithm and two widely-used reference methods. A vertex-wise assessment of the sulcal width is carried out by evaluating the correlation between sulcal width and age in a sample of an aging population, revealing clusters in the central, cingulate, and temporal sulcus regions associating wider sulci for older participants. The results confirm that the algorithm is reliable for obtaining sulcal width maps, allowing for vertex-wise analyses, and providing aggregated measures similar to the existing methods. The present algorithm is publicly available via https://github.com/HGGM-LIM/SWiM.

neuroscience↗

bioRxiv2022

ABLE: Automated Brain Lines Extraction Based on Laplacian Surface Collapse

The archetypical folded shape of the human cortex has been a long-standing topic for neuroscientific research. Nevertheless, the accurate neuroanatomical segmentation of sulci remains a challenge. Part of the problem is the uncertainty of where a sulcus transitions into a gyrus and vice versa. This problem can be avoided by focusing on sulcal fundi and gyral crowns which represent the topological opposites of cortical folding. We present Automated Brain Lines Extraction (ABLE), a method based on Laplacian surface collapse to segment sulcal fundi and gyral crown lines reliably. ABLE is built to work on standard FreeSurfer outputs, and eludes the delineation of anastomotic sulci while maintaining sulcal fundi lines that traverse the regions with the highest depth and curvature. First, it segments the cortex into gyral and sulcal surfaces; then, each surface is spatially filtered. A Laplacian-collapse-based algorithm is then applied to obtain a thinned representation of the surfaces. This surface is then used for careful detection of the endpoints of the lines. Finally, sulcal fundi and gyral crown lines are obtained by eroding the surfaces while preserving the connectivity between the endpoints. The method is validated by comparing ABLE with three other sulcal extraction methods using the Human Connectome Project (HCP) test-retest database to assess the reproducibility of the different tools. The results confirm ABLE as a reliable method to obtain sulcal lines with an accurate representation of the sulcal topology while ignoring anastomotic branches and the overestimation of the sulcal fundi lines. ABLE is publicly available via https://github.com/HGGM-LIM/ABLE.

neuroscience↗

bioRxiv2021

Additive, synergic and antagonistic interactions between maternal immune activation and peripubertal stress in cocaine addiction-like behaviour, morphofunctional brain parameters and striatal transcriptome.

Substance use disorders are more prevalent in schizophrenia, worsening its course and prognosis. Here, we used a double-hit rat model, combining maternal immune activation (MIA) and peripubertal stress (PUS), to study cocaine addiction and the underlying neurobehavioural alterations. We injected lipopolysaccharide or saline on gestational days 15 and 16 to pregnant rats. Their male offspring were then subjected to 5 episodes of unpredictable stress every other day during adolescence (from postnatal day 28 to 38). When rats reached adulthood, we studied cocaine addiction-like behaviour, impulsivity, conditioning processes and several aspects of brain structure and function by MRI, PET and RNAseq. MIA facilitated the acquisition of cocaine self-administration while PUS reduced cocaine intake, an effect that was reversed by MIA. MIA increased motivation for cocaine and reversed the effects of PUS during extended access. Incubation of seeking was unaffected. Neither hit alone nor their combination impacted Pavlovian or instrumental conditioning or impulsiveness. At the brain level, PUS reduced hippocampal volume and hyperactivated the dorsal subiculum. MIA+PUS altered the structure and function of the dorsal striatum increasing its volume and interfering with glutamatergic dynamics. MIA did not affect the gene expression of the nucleus accumbens but, when combined with PUS, modulated specific genes that could account for the restored cocaine intake. PUS had a profound effect on the dorsal striatal transcriptome however, this was obliterated when PUS occurred in animals with MIA. These results describe a complex interplay between MIA and stress on neurodevelopment and in the susceptibility to develop cocaine addiction.

neuroscience↗

bioRxiv2020

Testing The Role Of Δ9-Tetrahydrocannabinol During Adolescence As A Gateway Drug: Behavioural, Brain Imaging And Transcriptomic Studies

Cannabis is widely consumed by adolescents, and is also a potential prior step leading to the use of other drugs later in life (Gateway Hypothesis); however, the evidence for this hypothesis is controversial. This work aimed to increase our understanding of the long-term consequences of adolescent exposure to {Delta}9-tetrahydrocannabinol (THC) and to test the Gateway Hypothesis, experimentally. We exposed rats of both sexes to THC and studied its effects on reward-related processes, brain morphology (MRI), metabolism (1H-MRS), function (PET) and the transcriptomic profiles of the nucleus accumbens (RNASeq). Lastly, we studied cocaine-induced cellular activation (c-Fos) and cocaine addiction-like behaviours. THC exposure increased Pavlovian to instrumental transfer in males, goal-tracking (regardless of the sex) and impulsivity, but did not affect habit formation. Adolescent THC reduced striatal volume (in females), commissural integrity and ventricular volume. Also, there were lower levels of choline compounds in the cortex of THC-exposed rats and cerebellar hypoactivation in THC-females. THC also modified some of the gene expression programs of the nucleus accumbens, which could contribute to the behavioural features observed. Lastly, THC exposure increased cocaine-induced c-Fos levels in cortical and hypothalamic areas and increased the motivation for cocaine, followed by a higher rebound of use in THC-females after reestablishing low-effort conditions. Critically, acquisition of cocaine self-administration, compulsive seeking, intake under extended access or the incubation of seeking were unaltered. These results suggest that adolescent THC exposure alters psychological and brain development and that the Gateway Hypothesis does not entirely pass the test of preclinical enquiry.

neuroscience↗

bioRxiv2020

A drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent local relapse and treat established brain metastasis

Exclusion of brain metastases from clinical trials is a major cause of the limited therapeutic options for this growing population of cancer patients. Here, we report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to brain metastasis, we identified several hits from a library of FDA approved inhibitors and others being tested in clinical trials. A blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to organotypic cultures with metastases treated with the chaperone inhibitor revealed novel biomarkers in human brain metastasis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is fully compatible with human samples. We envision that METPlatform could be established as a clinically relevant strategy to personalize the management of metastatic disease in the brain and elsewhere. SummarySystemic spread of cancer continues to be the key aspect associated with lethality. In this publication, Zhu et al. describes a drug-screening platform specifically designed to study vulnerabilities of metastasis when colonizing secondary organs and demonstrates its value in difficult-to-treat brain metastasis using new models and patient-derived samples.

cancer biology↗