Emerging neuroscientific findings increasingly implicate lipidomic network destabilization as a proposed early-stage pathological mechanism underlying major depressive disorder (MDD), potentially bridging diverse pathological hypotheses. Current knowledge gaps persist regarding both neuroanatomical specificity and molecular signatures of lipid dysregulation in MDD pathogenesis. Our investigation employed spatial lipidomics through matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI), integrated with histomorphological assessments in a rat model featuring depressive-like phenotypes induced by multiple early life stress (mELS). Notably, we established the inaugural evidence of pan-encephalic lipid spatial reorganization in mELS rats, particularly within limbic-cortical circuitry nodes governing emotional processing. Systematic quantification across eight paired brain sections identified 17 lipid species with pronounced dyshomeostasis, demonstrating both inter-group (mELS vs. control) and intra-group (cross-regional) heterogeneity. Among these, distinct spatial patterns emerged: selective upregulation of phosphatidylcholine PC (39:6) localized to the amygdala (Section 7), contrasted with multi-regional elevations of phosphatidylglycerol PG (34:2) spanning the medial prefrontal cortex, insular cortex, and nucleus accumbens (Section 2). These results delineate lipid redistribution patterns driven by mELS across emotional circuits, establishing a spatial framework that correlates lipid dyshomeostasis with depression pathogenesis through integrated analysis of lipid spatial distribution and quantitative variation, thereby identifying key brain region-lipid relationships and informing targeted therapeutic development.
| Published in | Abstract Book of ICPHMS2025 & ICPBS2025 |
| Page(s) | 46-47 |
| Creative Commons |
This is an Open Access abstract, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2025. Published by Science Publishing Group |
Depressive Disorder, Lipid Dyshomeostasis, Mass Spectrometry Imaging, Spatial Omics
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