On-Tissue Spatial Proteomics Integrating MALDI-MS Imaging with Shotgun Proteomics Reveals Soy Consumption-Induced Protein Changes in a Fragile X Syndrome Mouse Model
Year: 2023
Type: article
Abstract: Fragile X syndrome (FXS), the leading cause of inherited intellectual disability and autism, is caused by the transcriptional silencing of the FMR1 gene, which encodes the fragile X messenger ribonucleoprotein (FMRP). FMRP interacts with numerous brain mRNAs that are involved in synaptic plasticity and implicated in autism spectrum disorders. Our published studies indicate that single-source, soy-based diets are associated with increased seizures and autism. Thus, there is an acute need for an unbiased protein marker identification in FXS in response to soy consumption. Herein, we present a spatial proteomics approach integrating mass spectrometry imaging with label-free proteomics in the FXS mouse model to map the spatial distribution and quantify levels of proteins in the hippocampus and hypothalamus brain regions. In total, 1250 unique peptides were spatially resolved, demonstrating the diverse array of peptidomes present in the tissue slices and the broad coverage of the strategy. A group of proteins that are known to be involved in glycolysis, synaptic transmission, and coexpression network analysis suggest a significant association between soy proteins and metabolic and synaptic processes in the Fmr1 KO brain. Ultimately, this spatial proteomics work represents a crucial step toward identifying potential candidate protein markers and novel therapeutic targets for FXS.
Source: ACS Chemical Neuroscience
Institution: University of Wisconsin–Madison
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Agriculture, Wisconsin Alumni Research Foundation, University of Wisconsin-Madison, National Institutes of Health, National Institute of Food and Agriculture, National Institute on Aging, National Institute of Mental Health, NIH Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, Division of Integrative Organismal Systems
Awards: Graduate Research Fellowship Program (GRFP), Acquisition of a High-Field Dual Source FTICR-MS for Pharmaceutical Research, G1803960457, G2075862466, G2118924489, G2388130288, G2708487702, G3055837027, TRTech-PGR: A mass spectrometric-based interdisciplinary approach to deciphering the molecular dialogue between between crop plants and their microbial friends and foes., G4837499102, G6019913678, G6484839831, Acquisition of a High Resolution High Speed MALDI Mass Spectrometer for Biomedical Research at UW-Madison, Acquisition of a Dual-Source, High-Performance, Ion Mobility, Quadrupole Time-of-Flight Mass Spectrometry System for Biomedical Research at UW-Madison, G822836364, G891322577, G9000105861, G9000127380, G9000131312, G9000197343, G9000231773
OpenAlex ID: W4389890946