PXD066497-1

PXD066497 is an original dataset announced via ProteomeXchange.

Title	Neuropeptides in the Extracellular Space of the Mouse Cortex Measured by In Vivo Nanodialysis Probe
Description	Neuropeptides are key neuromodulators in the central nervous system that shape sensory processing, yet their extracellular dynamics in the somatosensory cortex (S1) remain poorly understood. This study applies an innovative membrane-free silicon nanodialysis (ND) probe coupled with liquid chromatography-mass spectrometry (LC-MS) to analyze the extracellular neuropeptidome in the mouse S1 with spatial resolution down to 100 μm. Localized in vivo sampling identified extracellular peptides from secretogranin-1, ProSAAS, pro-opiomelanocortin (POMC), and others. Minimal tissue damage, enabled by probe dimensions of 75×15 μm², resulted in an absence of structural peptides in the dialysate indicating low intracellular contamination. Many detected secretory peptides correlated with strong local mRNA expression; however, the detection of POMC-derived peptides, despite negligible local expression, suggests long-distance peptide transport or extracellular processing. To expand peptide identification, a discovery-to-targeted peptidomic approach was developed, revealing 46 peptides from 24 proteins in dialysate samples, including 10 proteins with low local expression. Complementary S1 tissue analysis confirmed POMC peptides and showed that 17% of 304 prohormone-derived peptides had low local expression. These results uncover a complex extracellular peptide landscape shaped by both local and long-distance signaling. By overcoming the limitations of traditional microdialysis, this approach advances the understanding of neuropeptide signaling in cortical function.
HostingRepository	PRIDE
AnnounceDate	2025-09-29
AnnouncementXML	Submission_2025-09-28_16:09:40.510.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD066497
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Keyin Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	sulfated residue; amidated residue; 2-pyrrolidone-5-carboxylic acid (Glu); 2-pyrrolidone-5-carboxylic acid (Gln); phosphorylated residue; acetylated residue; monohydroxylated residue; deamidated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-23 21:05:31	ID requested
⏵ 1	2025-09-28 16:09:41	announced

10.6019/PXD066497;

10.1002/anie.202509490;

Li K, Shi W, Tan Y, Ding Y, Armstrong AG, Vlasov Y, Sweedler JV, Neuropeptides in the Extracellular Space of the Mouse Cortex Measured In Vivo by Nanodialysis Probe Coupled with LC-MS. Angew Chem Int Ed Engl, 64(39):e202509490(2025) [pubmed]

submitter keyword: PRM-PASEF, in vivo sampling,neuropeptides, DDA‑PASEF

Jonathan V. Sweedler
contact affiliation	Chemistry Department, University of Illinois Urbana-Champaign
contact email	jsweedle@illinois.edu
lab head
Keyin Li
contact affiliation	University of Illinois, Urbana-Champaign
contact email	keyinl2@illinois.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066497
     1. Label: PRIDE project
     2. Name: Neuropeptides in the Extracellular Space of the Mouse Cortex Measured by In Vivo Nanodialysis Probe