Multi-Omics Analyses to Detect Changes in the Mouse Hippocampus with Differences in Age, Diet and Strain

Grant Moen

Document Type

Article

Publication Date

8-7-2024

Keywords

JMG

JAX Location

In: Student Reports, Summer 2024, The Jackson Laboratory

Abstract

Recent advances have drastically improved the capabilities of mass spectrometry analysis, allowing for the generation of large datasets quantifying protein, lipid, and metabolite levels within biological tissues. We have leveraged these capabilities towards seeking new insights into how various modifiable and disease-related factors (diet, age, mutation status, learning) induce changes in the mouse brain, specifically the hippocampus, with whole-brain to single-cell resolution. These analyses are aimed at discovering novel therapeutic targets that RNA sequencing-based gene expression alone may not capture, such as faults in the proteostasis network that accumulate during aging and are hallmarks of neurodegenerative diseases like Alzheimer’s disease. We compared across age, strain, transgenic genotype, and behavioral conditioning to identify how these factors influence changes in the brain metabolome and proteome. We performed bulk proteomic and metabolomic analyses of the mouse hippocampus and hypothalamus and found strain-dependent and independent metabolite, protein, and pathway dysregulation between high- and low-fat diets. In parallel, we optimized a hippocampus cell dissociation protocol to generate cell samples suitable for single-cell proteomic analysis. This will aid in determining protein-function associations within the hippocampus and, when combined with mass spectrometry imaging, be used to create a single-cell proteomic atlas of the mouse hippocampus.

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