Evidence map›Paper›PMID 41698738›Full record

ArticleAnalytica chimica acta2026

Histology-guided spatial lipidomics and proteomics of the trisynaptic circuit in the human hippocampus.

Caitlin M Tressler, Lauren DeVine, Rahul Bharadwaj, Dalton R Brown, Daniel Weinberger, Kristine Glunde, Robert N Cole

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Analytica chimica acta, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Caitlin M TresslerThe Johns Hopkins University Applied Imaging Mass Spectrometry Core and Service Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; The Mass Spectrometry Imaging and Multi-Omics Shared Resource, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States. Electronic address: ctressl3@jh.edu.
Lauren DeVineThe Mass Spectrometry and Proteomics Facility, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States; The Mass Spectrometry Imaging and Multi-Omics Shared Resource, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States.
Rahul BharadwajLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, United States.
Dalton R BrownThe Johns Hopkins University Applied Imaging Mass Spectrometry Core and Service Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; The Mass Spectrometry Imaging and Multi-Omics Shared Resource, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States.
Daniel WeinbergerLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, United States; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Kristine GlundeThe Johns Hopkins University Applied Imaging Mass Spectrometry Core and Service Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States; The Mass Spectrometry Imaging and Multi-Omics Shared Resource, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States.
Robert N ColeThe Mass Spectrometry and Proteomics Facility, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States; The Mass Spectrometry Imaging and Multi-Omics Shared Resource, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, United States.

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin · 2006 to 2026
$33.2M
Johns Hopkins Institute for Clinical and Translational ResearchUM1TR004926 · NCATS · JOHNS HOPKINS UNIVERSITY · PI STEPHEN N. DAVIS, Daniel Ernest Ford · 2024 to 2026
$28.5M
Reprogramming of creatine metabolism in breast cancer metastasisR01CA264901 · NCI · JOHNS HOPKINS UNIVERSITY · PI Kristine Glunde · 2022 to 2026
$1.8M
NCATS NIH HHS UM1 TR004926NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA264901NIMH NIH HHS P30 MH075673
6 · The paper itself

Abstract

The human hippocampal trisynaptic circuit activity is essential for learning and memory. This canonical circuit has spatially distinct populations of neurons, but their unique contributions to neurodevelopment, as well as to dysfunction in neurodegenerative disorders, are missed when analyzing bulk tissue homogenates. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to guide laser capture microdissection (LCMD) of regions of interest for spatial multimodal analyses is a relatively new approach to study topographically distinct neuronal cell populations in heterogenous tissues. However, MALDI-MSI may not identify region-defining molecular mass-to-charge ions. Here, we apply a multimodal approach of MALDI-MSI-LCMD-lipidomic and proteomic analysis to the trisynaptic circuit. Our MALDI-MSI of the hippocampus revealed that the of mass-to-charge ions of the cornu ammonis 1 (CA1) and cornu ammonis 3 (CA3) did not segment from the surrounding tissue. Thus, we developed a novel histology-guided MALDI-MS imaging-LCMD-spatial lipidomic/proteomic pipeline with four steps which does not rely on segmentation analysis to determine and co-register regions of interest in tissue sections. Our pipeline allows MALDI imaging, LCMD, lipidomic and proteomic analysis from the same tissue section and does not require co-registration across serial sections. In addition, poly-l-lysine coating for improving tissue/cell adherence on indium-tin-oxide microscopy slides did not impact MALDI-MSI or spatial proteomics. We show that the human trisynaptic circuit proteomes of CA1 and CA3 pyramidal neurons are more similar to each other than those of the dentate gyrus (DG), which is consistent with previously reported transcriptomics studies. The spatial distributions of several phospholipids and proteins, however, were significantly different in cell bodies from the CA1, CA3 and DG regions, and these lipids correlated with some lipid metabolizing enzymes in those regions. As little is known about lipid metabolism in the hippocampus, our pipeline provides an initial step in studying the combined and differential spatial regulation of the lipids and proteins within the trisynaptic circuit that will provide insights into the development and disease-related molecular changes in these important hippocampal regions.

Indexed as

HippocampusLipidomicsProteomicsSynapsesHumansLaser Capture MicrodissectionSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationHippocampusHumanLipidomicLipidsMass spectrometryProteinsProteomicSingle cell typeTrisynaptic circuit

Identifiers

PMID41698738
PMCPMC13430514

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.