Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics

Area of Science:

• Neuroscience
• Proteomics
• Molecular Biology

Background:

• Traumatic brain injury (TBI) causes complex molecular changes, often missed by traditional tissue-level proteomic studies.
• Spatial proteomics enables analysis of sub-region-specific alterations within tissues, crucial for understanding TBI's heterogeneity.

Purpose of the Study:

• To investigate subregion-specific proteomic expression profiles in the mouse hippocampus at acute (1-day) and subacute (7-day) post-TBI phases.
• To identify region-specific vulnerabilities and long-term molecular consequences of TBI.

Main Methods:

• Hippocampal subregions were isolated using Laser Microdissection (LMD) from sham, 1-day post-TBI, and 7-day post-TBI mouse brains.
• Label-free quantitative proteomics was employed to analyze protein expression profiles.

Main Results:

• Spatial analysis identified region-specific protein changes, with elevated levels of FN1, LGALS3BP, HP, and MUG-1 in the stratum moleculare (SM), suggesting immune cell involvement.
• Upregulation of chronic traumatic encephalopathy markers (IGHM, B2M) was observed in the dentate gyrus bottom (DG2).
• Metabolic pathway analysis revealed disturbances in glucose/lipid metabolism and activated cholesterol synthesis, particularly in SM and deeper DG regions, indicating roles in neurogenesis and recovery.

Conclusions:

• Advanced spatial proteomics revealed dynamic, region-specific molecular responses in the hippocampus following TBI.
• The study identified region-specific vulnerabilities, dysregulated neuronal processes, and potential recovery pathways.
• Findings provide insights into TBI's neurological consequences, aiding biomarker discovery and therapeutic target identification.