Biology subjects

Todorov, M.

Publications and source records attributed to Todorov, M..

3 recordsLinked to original sources

bioRxiv2025

Multimodal synapse analysis reveals restricted integration of transplanted neurons remodeled by TREM2

Neuron transplantation offers a promising approach for circuit restoration after injury, but depends crucially on adequate synaptic integration. Yet, our knowledge of the effects of the host injury environment on transplanted neuron (tN) network integration remains limited. Here, we used a stab wound injury model to examine how tN synapses mature and integrate using multimodal read-outs. Morphological, ultrastructural and functional electrophysiological analysis of tN synapses indicated that tN integration and functional maturation are partially stunted. Spatial transcriptomics revealed persistent inflammatory signatures at the transplant site including Trem2 upregulation. Strikingly, in an environment devoid of TREM2, synaptic integration as well as functional maturation of tNs, including action potential maturation and spontaneous firing, were almost fully rescued. Spatial transcriptomics further showed reduced inflammatory pathways and improved maturation of tNs in Trem2-/- brains. This study highlights the importance of tackling chronic inflammation for adequate tN integration.

neuroscience↗

bioRxiv2024

Deep Learning and 3D Imaging Reveal Whole-Body Alterations in Obesity

Many diseases, such as obesity, have systemic effects that impact multiple organ systems throughout the body. However, tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking. Here, we developed a suite of deep learning-based image analysis algorithms (MouseMapper) and integrated it with tissue clearing and light-sheet microscopy to enable a comprehensive analysis of diseases impacting diverse systems across the mouse body. This approach enables the quantitative analysis of cellular and structural changes across the entire mouse body at unprecedented resolution and scale, including tracking nerves over several centimeters in whole animal bodies. To demonstrate its power, we applied MouseMapper to study nervous and immune systems in high-fat diet induced obesity. We uncovered widespread changes in both immune cell distribution and nerve structures, including alterations in the trigeminal nerve characterized by a reduced number of nerve endings in obese mice. These structural abnormalities were associated with functional deficits of whisker sensing and proteomic changes in the trigeminal ganglion, primarily affecting pathways related to axon growth and the complement system. Additionally, we found heterogeneity in obesity-induced whole-body inflammation across different tissues and organs. Our study demonstrates MouseMappers capability to discover and quantify pathological alterations at the whole-body level, offering a powerful approach for investigating the systemic impacts of various diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/608300v1_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@17d2601org.highwire.dtl.DTLVardef@14a2d3dorg.highwire.dtl.DTLVardef@e04114org.highwire.dtl.DTLVardef@d0b8b5_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe developed MouseMapper: AI-driven pipeline for whole-body structural analysis in mice C_LIO_LIMouseMapper revealed obesity-induced changes in nerves and immune cells across multiple organs C_LIO_LIMouseMapper identified facial nerve alterations in obesity linked to impaired whisker sensitivity C_LIO_LIMouseMapper has the potential for holistic 3D analysis of systemic diseases C_LI Supplementary Videos can be seen at: http://discotechnologies.org/MouseMapper/

systems biology↗

bioRxiv2023

Whole mouse body histology using standard IgG antibodies

Most diseases involve multiple interconnected physiological systems, but histological evaluation of their pathology is currently limited to small tissue samples. Here, we present wildDISCO, a technology that uses cholesterol extraction to enable deep tissue penetration of standard 150 kDa IgG antibodies in chemically fixed whole mice. Combining wildDISCO with whole mouse clearing, we generate whole-body maps of the nervous, immune, and lymphatic systems and show their close interactions throughout the mouse body. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/528921v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@f0de23org.highwire.dtl.DTLVardef@187fe94org.highwire.dtl.DTLVardef@15ac0faorg.highwire.dtl.DTLVardef@133703e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWildDISCO uses new tissue chemistry based on {beta}-cyclodextrin to enable histology in whole mouse bodies using full-size antibodies C_LIO_LIWildDISCO generates the first whole mouse body atlases for neurons, immune cells, blood and lymph vessels C_LIO_LIThe whole mouse atlases are available online to study the biological systems in health and disease C_LIO_LIVirtual Reality (VR) exploration of these atlases disentangles complex anatomical structures between organs and biological systems C_LI Supplementary Videos can be seen athttp://discotechnologies.org/wildDISCO/

biochemistry↗