Biology subjects

Garbelli, R.

Publications and source records attributed to Garbelli, R..

3 recordsLinked to original sources

bioRxiv2026

Different spatial profiles of aberrant N-glycans in pediatric and adult MOGHE brain tissue

Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a recently recognized epilepsy-associated lesion frequently linked to brain-restricted somatic variants in SLC35A2, a gene encoding the Golgi UDP-galactose transporter. Although previous studies demonstrated altered glycosylation in SLC35A2-mutated MOGHE tissue, the spatial relationship between glycosylation defects and histopathological abnormalities remains poorly understood. We applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) using formalin-fixed paraffin-embedded brain tissue from six histologically confirmed MOGHE cases (three pediatric and three adult) and three temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). We spatially evaluated N-glycan profiles across diagnostic tissue groups, with particular attention to molecular differences between lesional and perilesional regions and to recurrent abundance trends. All MOGHE cases harboured somatic SLC35A2 variants. Histologically, oligodendroglial hyperplasia and heterotopic neurons were present in all cases, while patchy hypomyelination was restricted to pediatric cases. Unsupervised spatial segmentation, integrated with neuropathological evaluation, revealed marked molecular heterogeneity in pediatric MOGHE. In these cases, lesional and perilesional regions were clearly distinguishable in both white matter (WM) and overlying grey matter (GM) boundaries patterns, whereas adult MOGHE and TLE-HS mainly showed a clearcut separation between WM and GM. Spatial analysis confirmed enrichment of the previously reported aberrant N-glycan species m/z 2094 and, to a lesser extent, m/z 2297 within MOGHE tissue, particularly in pediatric lesional WM. Notably, the distribution of m/z 2094 closely overlapped with areas of hypomyelination. Quantitative trajectory analysis of 151 detected N-glycan ions identified recurrent abundance profiles. Three representative spatial patterns emerged: pediatric lesion-enriched, pediatric perilesion-enriched, and TLE-HS-enriched profiles. Pediatric lesions were characterized by increased abundance of multiantennary glycans lacking terminal galactose residues and reduced abundance of galactosylated biantennary and multiantennary structures, consistent with defective UDP-galactose transport. In contrast, adult lesional and perilesional tissues exhibited largely overlapping glycomic profiles. These findings provide the first spatially resolved evidence that glycosylation abnormalities in SLC35A2-mutated MOGHE are closely associated with lesional pathology, particularly hypomyelination, and are substantially more pronounced in pediatric than adult cases. Spatial glycomics may therefore offer new insights into MOGHE pathophysiology and support the development of targeted therapeutic approaches aimed at correcting galactosylation defects.

neuroscience↗

bioRxiv2024

Quantitative cytoarchitectural phenotyping of deparaffinized human brain tissues

Advanced 3D imaging techniques and image segmentation and classification methods can profoundly transform biomedical research by offering deep insights into the cytoarchitecture of the human brain in relation to pathological conditions. Here, we propose a comprehensive pipeline for performing 3D imaging and automated quantitative cellular phenotyping on Formalin-Fixed Paraffin-Embedded (FFPE) human brain specimens, a valuable yet underutilized resource. We exploited the versatility of our method by applying it to different human specimens from both adult and pediatric, normal and abnormal brain regions. Quantitative data on neuronal volume, ellipticity, local density, and spatial clustering level were obtained from a machine learning-based analysis of the 3D cytoarchitectural organization of cells identified by different molecular markers in two subjects with malformations of cortical development (MCD). This approach will grant access to a wide range of physiological and pathological paraffin-embedded clinical specimens, allowing for volumetric imaging and quantitative analysis of human brain samples at cellular resolution. Possible genotype-phenotype correlations can be unveiled, providing new insights into the pathogenesis of various brain diseases and enlarging treatment opportunities.

neuroscience↗

bioRxiv2019

Same same but different: a web-based deep learning application for the histopathologic distinction of cortical malformations

We trained a convolutional neural network (CNN) to classify H.E. stained microscopic images of focal cortical dysplasia type IIb (FCD IIb) and cortical tuber of tuberous sclerosis complex (TSC). Both entities are distinct subtypes of human malformations of cortical development that share histopathological features consisting of neuronal dyslamination with dysmorphic neurons and balloon cells. The microscopic review of routine stainings of such surgical specimens remains challenging. A digital processing pipeline was developed for a series of 56 FCD IIb and TSC cases to obtain 4000 regions of interest and 200.000 sub-samples with different zoom and rotation angles to train a CNN. Our best performing network achieved 91% accuracy and 0.88 AUCROC (area under the receiver operating characteristic curve) on a hold-out test-set. Guided gradient-weighted class activation maps visualized morphological features used by the CNN to distinguish both entities. We then developed a web application, which combined the visualization of whole slide images (WSI) with the possibility for classification between FCD IIb and TSC on demand by our pretrained and build-in CNN classifier. This approach might help to introduce deep learning applications for the histopathologic diagnosis of rare and difficult-to-classify brain lesions.

pathology↗