PXD051093

PXD051093 is an original dataset announced via ProteomeXchange.

Title	Mapping Dynamic Molecular Changes in Hippocampal Subregions After Traumatic Brain Injury Through Spatial Proteomics
Description	Background: Traumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity and heterogeneity of the affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within tissues. This study focuses on the hippocampal sub-regions, analyzing proteomic expression profiles in mice at the acute (1 day) and subacute (7 days) phases of post-TBI to understand subregion-specific vulnerabilities and long-term consequences. Methods: Three mice brains were collected from each group including Sham, 1-day post-TBI and 7-day post-TBI. Hippocampal subregions were extracted using Laser Microdissection (LMD); and subsequently analyzed by label-free quantitative proteomics. Results: The spatial analysis reveals region-specific protein abundance changes, highlighting the elevation of FN1, LGALS3BP, HP, and MUG-1 in the stratum moleculare (SM), suggesting potential immune cell enrichment post-TBI. Notably, established markers of chronic traumatic encephalopathy, IGHM and B2M, exhibit specific upregulation in the dentate gyrus bottom (DG2) independent of direct mechanical injury. Metabolic pathway analysis identifies disturbances in glucose and lipid metabolism, coupled with activated cholesterol synthesis pathways enriched in SM at 7-Day post-TBI and subsequently in deeper DG1 and DG2 suggesting a role in neurogenesis and onset of recovery. Coordinated activation of neuroglia and microtubule dynamics in DG2 suggest recovery mechanisms in less affected regions. Cluster analysis revealed spatial variations post-TBI, indicative of dysregulated neuronal plasticity and neurogenesis and further predisposition to neurological disorders. TBI-induced protein upregulation (MUG-1, PZP, GFAP, TJP, STAT-1 and CD44) across hippocampal sub-regions indicates shared molecular responses and links to neurological disorders. Spatial variations were demonstrated by proteins dysregulated in both or either of the time-points exclusively in each subregion (ELAVL2, CLIC1 in PL, CD44 and MUG-1 in SM, and SHOC2, LGALS3 in DG). Conclusions: Utilizing advanced spatial proteomics techniques, the study unveils the dynamic molecular responses in distinct hippocampal subregions post-TBI. It uncovers region-specific vulnerabilities and dysregulated neuronal processes, and potential recovery-related pathways that contribute to our understanding of TBI’s neurological consequences and provides valuable insights for biomarker discovery and therapeutic targets.
HostingRepository	PRIDE
AnnounceDate	2024-06-23
AnnouncementXML	Submission_2024-06-23_01:42:05.627.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jia Fan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-29 13:31:44	ID requested
⏵ 1	2024-06-23 01:42:06	announced

10.1186/s12014-024-09485-6;

Maity S, Huang Y, Kilgore MD, Thurmon AN, Vaasjo LO, Galazo MJ, Xu X, Cao J, Wang X, Ning B, Liu N, Fan J, Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics. Clin Proteomics, 21(1):32(2024) [pubmed]

submitter keyword: Laser microdissection (LMD),LC-MS, hippocampus, Traumatic brain injury, acute and sub-acute phase, spatial proteomics

Jia Fan
contact affiliation	Assistant Professor, Biochemistry And Molecular Biology, School of Medicine, Tulane University
contact email	jfan5@tulane.edu
lab head
Jia Fan
contact affiliation	Tulane University
contact email	jfan5@tulane.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051093
     1. Label: PRIDE project
     2. Name: Mapping Dynamic Molecular Changes in Hippocampal Subregions After Traumatic Brain Injury Through Spatial Proteomics